/* Reset and Base Styles */ * { margin: 0; padding: 0; box-sizing: border-box; } html { scroll-behavior: smooth; } body { font-family: 'Inter', -apple-system, BlinkMacSystemFont, 'Segoe UI', Roboto, sans-serif; line-height: 1.6; color: #333; overflow-x: hidden; background: linear-gradient(135deg, #667eea 0%, #764ba2 100%); min-height: 100vh; } .container { max-width: 1200px; margin: 0 auto; padding: 0 20px; } /* Modern Glassmorphism Header */ .header { background: rgba(255, 255, 255, 0.1); backdrop-filter: blur(20px); -webkit-backdrop-filter: blur(20px); border: 1px solid rgba(255, 255, 255, 0.2); position: fixed; top: 0; left: 0; right: 0; z-index: 1000; transition: all 0.3s ease; box-shadow: 0 8px 32px rgba(0, 0, 0, 0.1); } .header-content { display: flex; align-items: center; justify-content: space-between; padding: 1rem 0; } .logo { display: flex; align-items: center; gap: 12px; } .logo-img { width: 40px; height: 40px; border-radius: 12px; box-shadow: 0 4px 16px rgba(0, 0, 0, 0.2); } .logo-text { font-size: 1.5rem; font-weight: 700; color: white; text-shadow: 0 2px 8px rgba(0, 0, 0, 0.3); } .nav { display: flex; gap: 2rem; } .nav-link { color: rgba(255, 255, 255, 0.9); text-decoration: none; font-weight: 500; transition: all 0.3s ease; position: relative; padding: 8px 16px; border-radius: 8px; } .nav-link:hover { color: white; background: rgba(255, 255, 255, 0.1); backdrop-filter: blur(10px); -webkit-backdrop-filter: blur(10px); } .cta-button-small { background: rgba(245, 158, 11, 0.9); backdrop-filter: blur(10px); -webkit-backdrop-filter: blur(10px); color: white; border: 1px solid rgba(255, 255, 255, 0.2); padding: 12px 24px; border-radius: 12px; font-weight: 600; cursor: pointer; transition: all 0.3s ease; box-shadow: 0 4px 16px rgba(245, 158, 11, 0.3); } .cta-button-small:hover { background: rgba(245, 158, 11, 1); transform: translateY(-2px); box-shadow: 0 8px 24px rgba(245, 158, 11, 0.4); } /* Hero Section with Enhanced Glassmorphism */ .hero { background: linear-gradient(135deg, #667eea 0%, #764ba2 50%, #3B5FBF 100%); color: white; padding: 140px 0 100px; position: relative; overflow: hidden; } .hero-bg { position: absolute; top: 0; left: 0; right: 0; bottom: 0; background: url('https://images.pexels.com/photos/3825586/pexels-photo-3825586.jpeg?auto=compress&cs=tinysrgb&w=1920&h=1080&fit=crop') center/cover; opacity: 0.1; z-index: 1; } .hero-content { display: grid; grid-template-columns: 1fr 1fr; gap: 4rem; align-items: center; position: relative; z-index: 2; } .hero-badge { display: inline-flex; align-items: center; gap: 8px; background: rgba(255, 255, 255, 0.15); backdrop-filter: blur(20px); -webkit-backdrop-filter: blur(20px); border: 1px solid rgba(255, 255, 255, 0.2); padding: 12px 20px; border-radius: 25px; font-size: 0.9rem; margin-bottom: 1.5rem; animation: fadeInUp 0.8s ease; box-shadow: 0 8px 32px rgba(0, 0, 0, 0.1); } .hero-title { font-size: 3.5rem; font-weight: 700; line-height: 1.1; margin-bottom: 1.5rem; animation: fadeInUp 0.8s ease 0.2s both; text-shadow: 0 4px 16px rgba(0, 0, 0, 0.3); } .highlight { background: linear-gradient(135deg, #F59E0B, #F97316); -webkit-background-clip: text; -webkit-text-fill-color: transparent; background-clip: text; filter: drop-shadow(0 2px 4px rgba(245, 158, 11, 0.3)); } .hero-description { font-size: 1.2rem; line-height: 1.6; opacity: 0.95; margin-bottom: 2rem; animation: fadeInUp 0.8s ease 0.4s both; text-shadow: 0 2px 8px rgba(0, 0, 0, 0.2); } .hero-stats { display: flex; gap: 2rem; margin-bottom: 2.5rem; animation: fadeInUp 0.8s ease 0.6s both; } .stat { text-align: center; background: rgba(255, 255, 255, 0.1); backdrop-filter: blur(15px); -webkit-backdrop-filter: blur(15px); border: 1px solid rgba(255, 255, 255, 0.2); padding: 20px; border-radius: 16px; box-shadow: 0 8px 32px rgba(0, 0, 0, 0.1); transition: transform 0.3s ease; } .stat:hover { transform: translateY(-4px); } .stat-number { display: block; font-size: 2rem; font-weight: 700; color: #F59E0B; text-shadow: 0 2px 8px rgba(245, 158, 11, 0.3); } .stat-label { font-size: 0.9rem; opacity: 0.9; } .hero-cta { display: flex; gap: 1rem; animation: fadeInUp 0.8s ease 0.8s both; } .cta-button-primary { background: rgba(245, 158, 11, 0.9); backdrop-filter: blur(15px); -webkit-backdrop-filter: blur(15px); color: white; border: 1px solid rgba(255, 255, 255, 0.2); padding: 18px 36px; border-radius: 16px; font-size: 1.1rem; font-weight: 600; cursor: pointer; display: flex; align-items: center; gap: 12px; transition: all 0.3s ease; box-shadow: 0 8px 32px rgba(245, 158, 11, 0.3); } .cta-button-primary:hover { background: rgba(245, 158, 11, 1); transform: translateY(-3px); box-shadow: 0 12px 40px rgba(245, 158, 11, 0.4); } .cta-button-secondary { background: rgba(255, 255, 255, 0.1); backdrop-filter: blur(15px); -webkit-backdrop-filter: blur(15px); color: white; border: 1px solid rgba(255, 255, 255, 0.3); padding: 16px 32px; border-radius: 16px; font-size: 1.1rem; font-weight: 600; cursor: pointer; display: flex; align-items: center; gap: 12px; transition: all 0.3s ease; box-shadow: 0 8px 32px rgba(0, 0, 0, 0.1); } .cta-button-secondary:hover { background: rgba(255, 255, 255, 0.2); transform: translateY(-2px); } .hero-visual { display: flex; justify-content: center; animation: fadeInRight 1s ease 0.4s both; } .hero-card { background: rgba(255, 255, 255, 0.15); backdrop-filter: blur(25px); -webkit-backdrop-filter: blur(25px); border: 1px solid rgba(255, 255, 255, 0.2); border-radius: 24px; padding: 28px; color: #333; box-shadow: 0 20px 60px rgba(0, 0, 0, 0.2); max-width: 380px; width: 100%; transition: transform 0.3s ease; } .hero-card:hover { transform: translateY(-8px); } .card-header { display: flex; justify-content: space-between; align-items: center; margin-bottom: 20px; } .card-title { font-weight: 600; color: rgba(255, 255, 255, 0.8); } .card-status { background: rgba(16, 185, 129, 0.9); backdrop-filter: blur(10px); -webkit-backdrop-filter: blur(10px); color: white; padding: 6px 16px; border-radius: 16px; font-size: 0.8rem; font-weight: 600; position: relative; border: 1px solid rgba(255, 255, 255, 0.2); } .card-status.live::before { content: ''; position: absolute; left: -8px; top: 50%; transform: translateY(-50%); width: 8px; height: 8px; background: #10B981; border-radius: 50%; animation: pulse 2s infinite; box-shadow: 0 0 8px rgba(16, 185, 129, 0.6); } .card-content h3 { font-size: 1.3rem; font-weight: 700; margin-bottom: 20px; color: white; text-shadow: 0 2px 8px rgba(0, 0, 0, 0.3); } .participants { display: flex; align-items: center; gap: 12px; margin-bottom: 20px; } .participant-avatars { display: flex; align-items: center; } .avatar { width: 36px; height: 36px; border-radius: 50%; background: linear-gradient(135deg, #3B5FBF, #1E3A8A); margin-left: -8px; border: 2px solid rgba(255, 255, 255, 0.8); box-shadow: 0 4px 12px rgba(0, 0, 0, 0.2); } .avatar:first-child { margin-left: 0; } .avatar-count { width: 36px; height: 36px; border-radius: 50%; background: rgba(255, 255, 255, 0.2); backdrop-filter: blur(10px); -webkit-backdrop-filter: blur(10px); color: white; display: flex; align-items: center; justify-content: center; font-size: 0.8rem; font-weight: 600; margin-left: -8px; border: 2px solid rgba(255, 255, 255, 0.3); } .participants span { color: rgba(255, 255, 255, 0.9); font-weight: 500; } .card-footer { display: flex; justify-content: space-between; padding-top: 20px; border-top: 1px solid rgba(255, 255, 255, 0.2); font-size: 0.9rem; color: rgba(255, 255, 255, 0.8); } /* About Section with Glass Cards */ .about-section { padding: 100px 0; background: linear-gradient(135deg, #f8fafc 0%, #e2e8f0 100%); position: relative; } .about-content { display: grid; grid-template-columns: 1fr 1fr; gap: 4rem; align-items: center; } .about-text h2 { font-size: 2.8rem; font-weight: 700; color: #1F2937; margin-bottom: 1.5rem; background: linear-gradient(135deg, #1F2937, #3B5FBF); -webkit-background-clip: text; -webkit-text-fill-color: transparent; background-clip: text; } .about-text p { font-size: 1.2rem; line-height: 1.7; color: #4B5563; margin-bottom: 2rem; } .about-features { display: flex; flex-direction: column; gap: 1rem; } .feature { display: flex; align-items: center; gap: 16px; font-weight: 500; color: #374151; background: rgba(255, 255, 255, 0.7); backdrop-filter: blur(15px); -webkit-backdrop-filter: blur(15px); padding: 16px 20px; border-radius: 12px; border: 1px solid rgba(255, 255, 255, 0.3); box-shadow: 0 4px 16px rgba(0, 0, 0, 0.1); transition: transform 0.3s ease; } .feature:hover { transform: translateX(8px); } .feature i { color: #10B981; font-size: 1.3rem; } .about-visual { display: flex; justify-content: center; } .meetings-card { background: rgba(59, 95, 191, 0.9); backdrop-filter: blur(20px); -webkit-backdrop-filter: blur(20px); border: 1px solid rgba(255, 255, 255, 0.2); border-radius: 24px; padding: 32px; color: white; max-width: 420px; width: 100%; box-shadow: 0 20px 60px rgba(59, 95, 191, 0.3); transition: transform 0.3s ease; } .meetings-card:hover { transform: translateY(-8px); } .meetings-header h3 { font-size: 1.4rem; font-weight: 700; margin-bottom: 24px; text-shadow: 0 2px 8px rgba(0, 0, 0, 0.2); } .meeting-item { display: flex; justify-content: space-between; align-items: center; padding: 20px 0; border-bottom: 1px solid rgba(255, 255, 255, 0.2); transition: background 0.3s ease; border-radius: 8px; margin: 0 -8px; padding-left: 8px; padding-right: 8px; } .meeting-item:hover { background: rgba(255, 255, 255, 0.1); } .meeting-item:last-child { border-bottom: none; } .meeting-title { font-weight: 600; font-size: 1rem; display: block; margin-bottom: 6px; } .meeting-details { display: flex; gap: 16px; font-size: 0.85rem; opacity: 0.9; } .meeting-status { width: 14px; height: 14px; border-radius: 50%; background: rgba(255, 255, 255, 0.3); } .meeting-status.active { background: #10B981; animation: pulse 2s infinite; box-shadow: 0 0 12px rgba(16, 185, 129, 0.6); } /* Benefits Section with Enhanced Glass Cards */ .benefits-section { padding: 100px 0; background: linear-gradient(135deg, #667eea 0%, #764ba2 100%); position: relative; } .section-header { text-align: center; margin-bottom: 4rem; } .section-header h2 { font-size: 2.8rem; font-weight: 700; color: white; margin-bottom: 1rem; text-shadow: 0 4px 16px rgba(0, 0, 0, 0.3); } .section-header p { font-size: 1.3rem; color: rgba(255, 255, 255, 0.9); text-shadow: 0 2px 8px rgba(0, 0, 0, 0.2); } .benefits-grid { display: grid; grid-template-columns: repeat(auto-fit, minmax(350px, 1fr)); gap: 2rem; } .benefit-card { background: rgba(255, 255, 255, 0.15); backdrop-filter: blur(25px); -webkit-backdrop-filter: blur(25px); border: 1px solid rgba(255, 255, 255, 0.2); border-radius: 20px; padding: 2.5rem; text-align: center; transition: all 0.3s ease; position: relative; overflow: hidden; box-shadow: 0 8px 32px rgba(0, 0, 0, 0.1); } .benefit-card::before { content: ''; position: absolute; top: 0; left: 0; right: 0; height: 4px; background: linear-gradient(135deg, #F59E0B, #F97316); transform: scaleX(0); transition: transform 0.3s ease; } .benefit-card:hover { transform: translateY(-12px); background: rgba(255, 255, 255, 0.2); box-shadow: 0 20px 60px rgba(0, 0, 0, 0.2); } .benefit-card:hover::before { transform: scaleX(1); } .benefit-icon { width: 72px; height: 72px; background: rgba(245, 158, 11, 0.9); backdrop-filter: blur(15px); -webkit-backdrop-filter: blur(15px); border: 1px solid rgba(255, 255, 255, 0.3); border-radius: 20px; display: flex; align-items: center; justify-content: center; margin: 0 auto 1.5rem; transition: transform 0.3s ease; box-shadow: 0 8px 24px rgba(245, 158, 11, 0.3); } .benefit-card:hover .benefit-icon { transform: scale(1.1) rotate(5deg); } .benefit-icon i { font-size: 1.6rem; color: white; } .benefit-card h3 { font-size: 1.4rem; font-weight: 700; color: white; margin-bottom: 1rem; text-shadow: 0 2px 8px rgba(0, 0, 0, 0.3); } .benefit-card p { color: rgba(255, 255, 255, 0.9); line-height: 1.6; margin-bottom: 1.5rem; text-shadow: 0 1px 4px rgba(0, 0, 0, 0.2); } .benefit-highlight { background: rgba(245, 158, 11, 0.9); backdrop-filter: blur(10px); -webkit-backdrop-filter: blur(10px); color: white; padding: 10px 20px; border-radius: 25px; font-weight: 600; font-size: 0.9rem; display: inline-block; border: 1px solid rgba(255, 255, 255, 0.2); box-shadow: 0 4px 16px rgba(245, 158, 11, 0.3); } /* Testimonials Section */ .testimonials-section { padding: 100px 0; background: linear-gradient(135deg, #f8fafc 0%, #e2e8f0 100%); } .testimonials-grid { display: grid; grid-template-columns: repeat(auto-fit, minmax(400px, 1fr)); gap: 2rem; margin-top: 3rem; } .testimonial-card { background: rgba(255, 255, 255, 0.8); backdrop-filter: blur(20px); -webkit-backdrop-filter: blur(20px); border: 1px solid rgba(255, 255, 255, 0.3); border-radius: 20px; padding: 2.5rem; box-shadow: 0 8px 32px rgba(0, 0, 0, 0.1); transition: transform 0.3s ease; } .testimonial-card:hover { transform: translateY(-8px); box-shadow: 0 20px 60px rgba(0, 0, 0, 0.15); } .testimonial-content { margin-bottom: 1.5rem; } .quote-icon { font-size: 3.5rem; color: #3B5FBF; opacity: 0.3; line-height: 1; margin-bottom: 1rem; } .testimonial-content p { font-size: 1.2rem; line-height: 1.6; color: #4B5563; font-style: italic; } .testimonial-author { display: flex; justify-content: space-between; align-items: center; } .author-info h4 { font-weight: 700; color: #1F2937; margin-bottom: 4px; } .author-info span { color: #6B7280; font-size: 0.9rem; } .rating { color: #F59E0B; filter: drop-shadow(0 2px 4px rgba(245, 158, 11, 0.3)); } /* Events Section */ .events-section { padding: 100px 0; background: linear-gradient(135deg, #1F2937 0%, #111827 100%); color: white; position: relative; } .events-content { text-align: center; } .events-text h2 { font-size: 2.8rem; font-weight: 700; margin-bottom: 1rem; text-shadow: 0 4px 16px rgba(0, 0, 0, 0.3); } .events-text p { font-size: 1.3rem; opacity: 0.9; margin-bottom: 2rem; text-shadow: 0 2px 8px rgba(0, 0, 0, 0.2); } .urgency-banner { background: rgba(245, 158, 11, 0.9); backdrop-filter: blur(15px); -webkit-backdrop-filter: blur(15px); border: 1px solid rgba(255, 255, 255, 0.2); padding: 16px 32px; border-radius: 30px; display: inline-flex; align-items: center; gap: 12px; font-weight: 600; margin-bottom: 3rem; animation: pulse 2s infinite; box-shadow: 0 8px 32px rgba(245, 158, 11, 0.3); } .events-list { display: grid; grid-template-columns: repeat(auto-fit, minmax(350px, 1fr)); gap: 2rem; margin-top: 3rem; } .event-card { background: rgba(255, 255, 255, 0.1); backdrop-filter: blur(20px); -webkit-backdrop-filter: blur(20px); border: 1px solid rgba(255, 255, 255, 0.2); border-radius: 20px; padding: 2.5rem; text-align: left; transition: all 0.3s ease; box-shadow: 0 8px 32px rgba(0, 0, 0, 0.1); } .event-card:hover { background: rgba(255, 255, 255, 0.15); transform: translateY(-8px); box-shadow: 0 20px 60px rgba(0, 0, 0, 0.2); } .event-icon { width: 56px; height: 56px; background: rgba(59, 95, 191, 0.9); backdrop-filter: blur(10px); -webkit-backdrop-filter: blur(10px); border: 1px solid rgba(255, 255, 255, 0.2); border-radius: 16px; display: flex; align-items: center; justify-content: center; margin-bottom: 1.5rem; box-shadow: 0 4px 16px rgba(59, 95, 191, 0.3); } .event-icon i { color: white; font-size: 1.3rem; } .event-info h3 { font-size: 1.3rem; font-weight: 700; margin-bottom: 0.5rem; text-shadow: 0 2px 8px rgba(0, 0, 0, 0.2); } .event-info p { opacity: 0.9; margin-bottom: 1.5rem; } .event-cta { background: rgba(245, 158, 11, 0.9); backdrop-filter: blur(10px); -webkit-backdrop-filter: blur(10px); color: white; border: 1px solid rgba(255, 255, 255, 0.2); padding: 14px 28px; border-radius: 12px; font-weight: 600; cursor: pointer; transition: all 0.3s ease; width: 100%; box-shadow: 0 4px 16px rgba(245, 158, 11, 0.3); } .event-cta:hover { background: rgba(245, 158, 11, 1); transform: translateY(-2px); box-shadow: 0 8px 24px rgba(245, 158, 11, 0.4); } /* CTA Section with Glass Form */ .cta-section { padding: 100px 0; background: linear-gradient(135deg, #667eea 0%, #764ba2 100%); color: white; } .cta-content { display: grid; grid-template-columns: 1fr 1fr; gap: 4rem; align-items: start; } .cta-text h2 { font-size: 2.8rem; font-weight: 700; color: white; margin-bottom: 1.5rem; text-shadow: 0 4px 16px rgba(0, 0, 0, 0.3); } .cta-text p { font-size: 1.3rem; color: rgba(255, 255, 255, 0.9); line-height: 1.6; margin-bottom: 2rem; text-shadow: 0 2px 8px rgba(0, 0, 0, 0.2); } .trust-indicators { display: flex; flex-direction: column; gap: 1rem; } .indicator { display: flex; align-items: center; gap: 12px; color: rgba(255, 255, 255, 0.9); font-weight: 500; background: rgba(255, 255, 255, 0.1); backdrop-filter: blur(10px); -webkit-backdrop-filter: blur(10px); padding: 12px 16px; border-radius: 12px; border: 1px solid rgba(255, 255, 255, 0.2); } .indicator i { color: #10B981; font-size: 1.2rem; } .cta-form { background: rgba(255, 255, 255, 0.15); backdrop-filter: blur(25px); -webkit-backdrop-filter: blur(25px); border: 1px solid rgba(255, 255, 255, 0.2); border-radius: 24px; padding: 2.5rem; box-shadow: 0 20px 60px rgba(0, 0, 0, 0.2); } .brochure-form h3 { font-size: 1.6rem; font-weight: 700; color: white; margin-bottom: 1.5rem; text-align: center; text-shadow: 0 2px 8px rgba(0, 0, 0, 0.3); } .form-row { display: grid; grid-template-columns: 1fr 1fr; gap: 1rem; margin-bottom: 1rem; } .form-group { margin-bottom: 1rem; } .form-group label { display: block; font-weight: 500; color: rgba(255, 255, 255, 0.9); margin-bottom: 0.5rem; text-shadow: 0 1px 4px rgba(0, 0, 0, 0.2); } .form-group input[type="text"], .form-group input[type="email"], .form-group input[type="tel"] { width: 100%; padding: 14px 18px; border: 1px solid rgba(255, 255, 255, 0.3); border-radius: 12px; font-size: 1rem; transition: all 0.3s ease; background: rgba(255, 255, 255, 0.1); backdrop-filter: blur(10px); -webkit-backdrop-filter: blur(10px); color: white; } .form-group input::placeholder { color: rgba(255, 255, 255, 0.6); } .form-group input:focus { outline: none; border-color: rgba(245, 158, 11, 0.8); background: rgba(255, 255, 255, 0.15); box-shadow: 0 0 20px rgba(245, 158, 11, 0.3); } .form-group label input[type="checkbox"] { margin-right: 8px; accent-color: #F59E0B; } .submit-button { width: 100%; background: rgba(245, 158, 11, 0.9); backdrop-filter: blur(15px); -webkit-backdrop-filter: blur(15px); color: white; border: 1px solid rgba(255, 255, 255, 0.2); padding: 18px 24px; border-radius: 16px; font-size: 1.2rem; font-weight: 600; cursor: pointer; display: flex; align-items: center; justify-content: center; gap: 12px; transition: all 0.3s ease; margin-bottom: 1rem; box-shadow: 0 8px 32px rgba(245, 158, 11, 0.3); } .submit-button:hover { background: rgba(245, 158, 11, 1); transform: translateY(-2px); box-shadow: 0 12px 40px rgba(245, 158, 11, 0.4); } .form-note { font-size: 0.9rem; color: rgba(255, 255, 255, 0.8); text-align: center; text-shadow: 0 1px 4px rgba(0, 0, 0, 0.2); } /* Animations */ @keyframes fadeInUp { from { opacity: 0; transform: translateY(30px); } to { opacity: 1; transform: translateY(0); } } @keyframes fadeInRight { from { opacity: 0; transform: translateX(30px); } to { opacity: 1; transform: translateX(0); } } @keyframes pulse { 0%, 100% { transform: scale(1); opacity: 1; } 50% { transform: scale(1.05); opacity: 0.8; } } /* Responsive Design */ @media (max-width: 768px) { .container { padding: 0 16px; } .header-content { flex-direction: column; gap: 1rem; padding: 0.5rem 0; } .nav { gap: 1rem; flex-wrap: wrap; justify-content: center; } .hero { padding: 120px 0 80px; } .hero-content { grid-template-columns: 1fr; gap: 2rem; text-align: center; } .hero-title { font-size: 2.5rem; } .hero-stats { justify-content: center; flex-wrap: wrap; } .hero-cta { flex-direction: column; align-items: center; } .cta-button-primary, .cta-button-secondary { width: 100%; justify-content: center; } .about-content { grid-template-columns: 1fr; gap: 2rem; } .about-text { order: 2; } .about-visual { order: 1; } .benefits-grid { grid-template-columns: 1fr; } .testimonials-grid { grid-template-columns: 1fr; } .events-list { grid-template-columns: 1fr; } .cta-content { grid-template-columns: 1fr; gap: 2rem; } .form-row { grid-template-columns: 1fr; } .section-header h2, .cta-text h2, .events-text h2 { font-size: 2.2rem; } .about-text h2 { font-size: 2.2rem; } } @media (max-width: 480px) { .hero-title { font-size: 2rem; } .benefit-card { padding: 1.5rem; } .hero-stats { flex-direction: column; align-items: center; } .stat { margin-bottom: 1rem; } }

Abstract Number: S193

CARFILZOMIB, LENALIDOMIDE, AND DEXAMETHASONE (KRD) AS MAINTENANCE THERAPY AFTER AUTOLOGOUS STEM-CELL TRANSPLANTATION (ASCT) IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM)

Presenter: Dominik Dytfeld
Session: Long term follow-up of clinical trials in lymphoid malignancies (CLL/LGL/MM)

Abstract Summary:

KRd maintenance therapy significantly improved progression-free survival (PFS) compared to lenalidomide (R) alone in patients with newly diagnosed multiple myeloma (NDMM) post-ASCT, with a 4-year PFS of 67.5% vs 38.0% and a hazard ratio (HR) of 0.46.
Overall survival (OS) was also superior with KRd, showing a 4-year OS of 84.3% compared to 79.2% for R, with an HR of 0.49, indicating a significant survival advantage.
KRd achieved deeper and more sustained responses, with a higher rate of MRD negativity and complete response (73% vs 51%) and 12-month sustained MRD-negativity (49% vs 28%).
Time to progression on second-line therapy (PFS2) was longer with KRd, with a median not reached compared to 77.3 months for R, suggesting prolonged disease control.
KRd was associated with a higher incidence of serious adverse events, but fewer patients discontinued therapy compared to R, supporting its potential as a new standard of care for NDMM post-ASCT.

Clinical relevance: Practice Changing

Given the robust evidence from a well-conducted phase 3 RCT, the significant improvement in survival outcomes, and the feasibility of integrating KRd into current treatment protocols, these findings are strong enough to warrant a change in clinical practice for the maintenance treatment of newly diagnosed multiple myeloma patients post-ASCT. However, outside of the US the cost of treatment is likely to limit its usage.

Link to Abstract S193

Abstract Number: PS1737

UPDATED COMPARATIVE EFFECTIVENESS OF TALQUETAMAB VS REAL-WORLD PHYSICIAN'S CHOICE OF TREATMENT IN LOCOMMOTION AND MOMMENT FOR PATIENTS WITH TRIPLE-CLASS EXPOSED RELAPSED/REFRACTORY MULTIPLE MYELOMA

Presenter: Hermann Einsele
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Talquetamab (Tal) demonstrated significantly higher overall response rates (ORR) compared to real-world physician’s choice (RWPC) in triple-class exposed relapsed/refractory multiple myeloma (TCE RRMM), with ORRs of 74.1% for weekly dosing and 69.5% for bi-weekly dosing versus 29.9% and 29.2% for RWPC, respectively (P<0.0001).
Patients receiving Tal had markedly higher rates of very good partial response or better (≥VGPR) and complete response or better (≥CR) compared to RWPC, with ≥VGPR rates of 59.4% and 59.1% for weekly and bi-weekly dosing, respectively, and ≥CR rates of 32.9% and 40.3% (P<0.0001).
Tal treatment significantly reduced the risk of progression or death, with hazard ratios (HR) of 0.54 for weekly dosing and 0.48 for bi-weekly dosing compared to RWPC (P<0.0001).
Time to next treatment (TTNT) was significantly longer for Tal, with HRs of 0.51 for weekly and 0.46 for bi-weekly dosing (P<0.0001).
Tal treatment resulted in a substantial reduction in the risk of death, with HRs of 0.38 for weekly and 0.34 for bi-weekly dosing (P<0.0001), confirming its clinical benefit in TCE RRMM.

Clinical relevance: Practice Changing

Given the robust evidence, significant improvement in clinical outcomes, and the feasibility of integrating Talquetamab into current treatment protocols, these findings are strong enough to warrant a change in clinical practice for the treatment of triple-class exposed relapsed/refractory multiple myeloma.

Link to Abstract PS1737

Abstract Number: PS1712

DARATUMUMAB + BORTEZOMIB/LENALIDOMIDE/DEXAMETHASONE IN TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA: ANALYSIS OF SUSTAINED MINIMAL RESIDUAL DISEASE NEGATIVITY IN THE PHASE 3 PERSEUS TRIAL

Presenter: Prof. Philippe Moreau
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

DVRd induction/consolidation plus DR maintenance achieved ≥12-month sustained MRD negativity in 64.8% of patients versus 29.7% with VRd plus R maintenance; ≥24-month sustained MRD negativity was 55.8% vs 22.6%.
Patients with ≥12-month sustained MRD negativity had >95% 48-month PFS, regardless of treatment arm.
DVRd reduced functionally high-risk rates (progression ≤18 months) to 3.1% compared to 6.8% with VRd; combined functionally high risk or preprogression deaths were 5.4% vs 11.0% in the first 18 months.
Benefits of DVRd were consistent across subgroups, including age ≥65 and high-risk cytogenetics.
Data support DVRd plus DR maintenance as a standard of care for transplant-eligible NDMM, as reflected in NCCN recommendations.

Abstract: PS1712

Clinical relevance: Important but Not Practice Changing>

Given the robust, mature data from a large phase 3 RCT, the clear superiority of DVRd/DR over VRd/R in achieving sustained MRD negativity and PFS, and the alignment with evolving guidelines, these findings are practice-changing for the frontline management of transplant-eligible NDMM.

Link to Abstract PS1712

Abstract Number: PS1723

CILTACABTAGENE AUTOLEUCEL VERSUS STANDARD OF CARE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: CARTITUDE-4 SURVIVAL SUBGROUP ANALYSES

Presenter: Yael Cohen
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival (PFS) and overall survival (OS) compared to standard of care (SOC) in relapsed and lenalidomide-refractory multiple myeloma, with a hazard ratio for PFS of 0.29 and for OS of 0.55 at 33.6 months median follow-up.
PFS and OS benefits with cilta-cel were consistent across subgroups, including patients with standard-risk and high-risk cytogenetics (del(17p), t(4;14), t(14;16), gain/amp(1q)), and those with extramedullary disease.
In patients with extramedullary disease, median PFS was 13 months with cilta-cel versus 4 months with SOC; median OS was not reached with cilta-cel versus 16 months with SOC.
Across 1, 2, or 3 prior lines of therapy, median PFS was not reached with cilta-cel versus 17, 12, and 8 months with SOC, respectively; OS hazard ratios favored cilta-cel in all groups.
Cilta-cel may overcome poor prognosis associated with high-risk cytogenetics and supports a positive benefit-risk profile as early as after first relapse.

Clinical relevance: Important but Not Practice Changing

In summary, the CARTITUDE-4 subgroup analyses provide robust, generalizable evidence that cilta-cel offers superior efficacy over current standard regimens in lenalidomide-refractory multiple myeloma, including high-risk populations. These findings warrant immediate consideration for incorporation into clinical practice.

Link to Abstract PS1723

Abstract Number: PS1730

DARATUMUMAB PLUS BORTEZOMIB, LENALIDOMIDE, AND DEXAMETHASONE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA: SUBGROUP ANALYSIS OF TRANSPLANT-INELIGIBLE PATIENTS IN THE PHASE 3 CEPHEUS STUDY

Presenter: Prof. Thierry Facon
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Daratumumab plus VRd (DVRd) significantly improved MRD-negativity rates at 10⁻⁵ (60.4% vs 39.3%; OR 2.37; P<0.0001) and at 10⁻⁶ (45.8% vs 26.9%; OR 2.28; P=0.0010) compared to VRd in transplant-ineligible NDMM patients.
Sustained MRD-negativity (≥12 months) was higher with DVRd (46.5% vs 27.6%; OR 2.27; P=0.0010).
≥Complete response (CR) rate was superior with DVRd (80.6% vs 61.4%; OR 2.73; P<0.0001).
Median progression-free survival (PFS) was not reached for DVRd and was 49.6 months for VRd (HR 0.51; P=0.0003); 54-month PFS rate was 69.0% vs 48.0%.
Overall survival favored DVRd (HR 0.66; after censoring COVID-19 deaths, HR 0.55), and safety was consistent with known profiles.

Clinical relevance: Important but Not Practice Changing

Given the robust, mature data from a phase 3 RCT, the significant and clinically meaningful improvements in depth of response and PFS, and the alignment with evolving global standards, these findings warrant immediate consideration for incorporation into clinical practice for transplant-ineligible NDMM patients.

Link to Abstract PS1730

Abstract Number: S100

FIRST-IN-HUMAN STUDY OF JNJ-79635322 (JNJ-5322), A NOVEL, NEXT-GENERATION TRISPECIFIC ANTIBODY, IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: INITIAL PHASE 1 RESULTS

Presenter: Dr. Rakesh Popat
Session: Plenary Abstracts Session

Abstract Summary:

JNJ-5322, a trispecific antibody targeting BCMA and GPRC5D, achieved a 100% overall response rate (ORR) at the recommended phase 2 dose (RP2D, 100 mg Q4W) in anti-BCMA/-GPRC5D naïve relapsed/refractory multiple myeloma patients, with 89% achieving ≥VGPR; all remain in response at median follow-up of 8.5 months.
Across all response-evaluable patients, ORR was 73% (66% ≥VGPR), and at the RP2D, ORR was 86% (75% ≥VGPR).
Safety profile showed mostly grade 1/2 cytokine release syndrome (CRS, 59%; no grade ≥3), low rates of ICANS (2%, all grade 1), and manageable grade 3/4 infection rates (28%); GPRC5D-associated adverse events (nail/taste/skin) were frequent but primarily grade 1/2.
JNJ-5322 demonstrated improved tolerability compared to anti-GPRC5D bispecifics and offers off-the-shelf, outpatient, Q4W dosing, suggesting a potential paradigm shift with efficacy comparable to CAR-T therapies.

Clinical relevance: Interesting but Limited Impact

In summary, while the early efficacy and safety profile of JNJ-5322 are promising and the trispecific approach is innovative, the data are preliminary and not yet sufficient to influence clinical practice or challenge current standards. Larger, randomized studies with longer follow-up are needed to establish its true clinical value.

Link to Abstract S100

Abstract Number: S186

MULTIOMICS CHARACTERIZATION OF MINIMAL RESIDUAL DISEASE (MRD) KINETICS IN MULTIPLE MYELOMA (MM) PATIENTS REVEALS THAT EARLY IMMUNOTHERAPY INTERCEPTION DRIVES CLINICAL BENEFIT IN EXPERIMENTAL MODELS

Presenter: Noelia Collado-Gisbert
Session: Myeloma and other monoclonal gammopathies - Biology & translational research

Abstract Summary:

MRD kinetics were identified as a critical prognostic factor in MM, with three subgroups showing distinct PFS rates at 6 years: sustained undetected MRD (83%), positive/stable (74%), and positive/increasing (11%), outperforming traditional risk stratification methods.
MRD cells retained most CNAs and a significant portion of somatic mutations post-induction and transplant, with progressive genomic evolution observed from diagnosis to MRD and relapse stages.
MRD cells exhibited significant transcriptional changes related to immune response, with altered distributions of various immune cell types from diagnosis to post-treatment MRD stages.
In MIcγ1^huCRBN mice, early immunotherapy MRD interception with anti-BCMA CAR T cells significantly improved OS compared to treatment at relapse (12.2 vs 9.5 months), highlighting the potential clinical benefit of early intervention.
The study suggests that early MRD-targeted immunotherapy could be a promising strategy for improving outcomes in MM, warranting further investigation in clinical trials.

Clinical relevance: Important but Not Practice Changing

Overall, the study offers significant insights into MRD kinetics and resistance in MM, suggesting potential future directions for clinical trials. However, the findings are not yet sufficient to change current clinical practice without further validation and exploration in human clinical trials.

Link to Abstract S186

Abstract Number: S187

IN MULTIPLE MYELOMA, DEL17P CONFERS VULNERABILITY TO THE INHIBITION OF PKMYT1 KINASE.

Presenter: Anaïs Schavgoulidze
Session: Myeloma and other monoclonal gammopathies - Biology & translational research

Abstract Summary:

PKMYT1 kinase was identified as a key dependency in multiple myeloma (MM) cells with del17p, showing overexpression in these cells and correlating with poor overall survival.
Genetic depletion of PKMYT1 led to decreased CDK1 phosphorylation and reduced cell viability, particularly in del17p MM cell lines.
RP-6306, a selective PKMYT1 inhibitor, induced CDK1 hyperactivation and significantly decreased cell viability in del17p and/or TP53-mutated MM cells, causing apoptosis and cell cycle arrest.
Inhibition of PKMYT1 resulted in replication stress, DNA damage, and mitotic catastrophe specifically in del17p MM cell lines, with no significant toxicity in healthy bone marrow cells.
In vivo studies demonstrated that RP-6306 treatment reduced tumor volume and prolonged survival in mice with del17p MM, highlighting PKMYT1 as a potential therapeutic target for high-risk MM patients.

Clinical relevance: Important but Not Practice Changing

While the study provides valuable insights into a novel therapeutic target for del17p MM, the findings are not yet sufficient to change clinical practice. Further clinical trials are necessary to confirm these results and determine the practical application of RP-6306 in treating MM patients.

Link to Abstract S187

Abstract Number: S192

LONG-TERM (≥5 YEAR) REMISSION AND SURVIVAL AFTER TREATMENT WITH CILTACABTAGENE AUTOLEUCEL IN CARTITUDE-1 PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA

Presenter: Prof. Dr. Sundar Jagannath
Session: Long term follow-up of clinical trials in lymphoid malignancies (CLL/LGL/MM)

Abstract Summary:

At a median follow-up of 60.3 months, 33% of patients treated with a single cilta-cel infusion remained alive and progression free for ≥5 years without further multiple myeloma therapy.
Median overall survival for the entire cohort (N=97) was 60.6 months, substantially exceeding historical expectations for heavily pretreated relapsed/refractory multiple myeloma.
Patients progression free ≥5 years included those with high-risk cytogenetics and extramedullary disease, with baseline characteristics comparable to those with earlier progression.
Correlative analyses identified higher naive T cell fractions in the drug product, lower neutrophil-to-T-cell ratio, higher baseline hemoglobin/platelets, and higher effector-to-target ratio as biomarkers associated with long-term remission.
All 12 patients at a single center who were progression free ≥5 years were MRD negative at 10^–6 and imaging negative by PET/CT for 5 years, supporting deep and durable responses.

Clinical relevance: Important but Not Practice-Changing

In summary, this study provides highly meaningful long-term efficacy data for cilta-cel in RRMM, suggesting the possibility of durable remission in a subset of patients. While the results are impressive and reinforce the value of CAR-T in this setting, the lack of a control arm, limited generalizability, and current access barriers mean these findings are important but not yet practice-changing.

Link to Abstract S192

Abstract Number: S194

CARFILZOMIB INDUCTION, CONSOLIDATION, AND MAINTENANCE WITH OR WITHOUT AUTOLOGOUS STEM-CELL TRANSPLANT: LONG-TERM FOLLOW-UP OF THE RANDOMISED, PHASE 2 FORTE TRIAL

Presenter: Francesca Gay
Session: Long term follow-up of clinical trials in lymphoid malignancies (CLL/LGL/MM)

Abstract Summary:

KRd-ASCT demonstrated a median PFS of 99 months, significantly longer than KRd12 (70 months) and KCd-ASCT (64 months), with hazard ratios of 0.73 and 0.65, respectively.
KRd-ASCT showed a trend towards superior PFS2 compared to KRd12 and KCd-ASCT, with hazard ratios of 0.71 and 0.72, although not statistically significant.
Median TTNT was not reached at 8 years in the KRd-ASCT arm, significantly better than KRd12 and KCd-ASCT, with hazard ratios of 0.59 and 0.63, respectively.
KR maintenance for 2 years provided significant PFS benefits over R alone, particularly up to 4 years from R2, with a 4-year PFS of 75% versus 66% and a hazard ratio of 0.66.
The incidence of secondary primary malignancies was 6%, higher in patients who underwent ASCT, with a relative incidence of 1.99 compared to KRd12 and 1.48 compared to KCd-ASCT.

Clinical relevance: Important but Not Practice Changing

While the study provides valuable insights into the potential benefits of KRd-ASCT in improving PFS, the lack of a significant OS advantage and the safety concerns regarding SPMs suggest that these findings, although important, do not yet warrant a change in clinical practice. Further research is needed to confirm these results and address safety issues.

Link to Abstract S194

Abstract Number: S196

ELEVATED CIRCULATING TUMOR CELL (CTC) NUMBERS ASSOCIATE WITH A HIGHLY PROLIFERATIVE (PR) AND GENOMICALLY COMPLEX PHENOTYPE IN NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM) PATIENTS

Presenter: Juan-Jose Garces
Session: New prognostic features in plasma cell disorders

Abstract Summary:

Elevated circulating tumor cells (CTCs) at baseline are associated with shorter progression-free survival (PFS) and overall survival (OS) in newly diagnosed multiple myeloma (NDMM) patients, with ≤10 CTCs indicating outstanding OS.
High CTC levels correlate with high bone marrow infiltration and high-risk clinical features such as ISS3 and elevated LDH, and are linked to complex genomic subgroups like NSD2_Gain/Amp1q_Del13q and MAF_HyperAPOBEC.
CTCs are strongly associated with high-risk genomic features, including chromothripsis, gain/amp1q, APOBEC mutagenesis, and MAF translocations, with a cutoff of 1000 CTCs independently predicting PFS and OS.
Transcriptomic analysis reveals 210 genes positively correlated with CTCs, enriched in proliferation and cell cycle functions, while 452 genes negatively associated with CTCs are enriched in migration and immune activation.
CTC enumeration, when combined with genomic classification, may enhance risk stratification in MM, reflecting disease with increased circulating potential, higher proliferative activity, and genomic complexity.

Clinical relevance: Important but Not Practice Changing

Overall, while the study offers important insights into the prognostic value of CTCs in MM and suggests potential improvements in risk stratification, it does not yet provide evidence strong enough to change current clinical practice. Further research and validation are needed to establish CTC enumeration as a standard component of MM management.

Link to Abstract S196

Abstract Number: S199

CIRCULATING TUMOR CELLS FOR THE STAGING OF MULTIPLE MYELOMA: A EUROPEAN POOLED ANALYSIS OF 2446 NEWLY DIAGNOSED PATIENTS

Presenter: Dr. Luca Bertamini
Session: New prognostic features in plasma cell disorders

Abstract Summary:

Logarithmic increments of circulating tumor cell (CTC) levels in newly diagnosed multiple myeloma (NDMM) patients identified five subgroups with significantly different median progression-free survival (PFS), ranging from 77 months for CTC≤0.001% to 16 months for CTC≥1% (p<0.0001).
High CTC levels were strongly correlated with inferior PFS (HR 1.18, 95% CI 1.12-1.24, p<0.001), independent of the Revised International Staging System, 1q gain/amp, and induction regimen, adjusting for transplant eligibility.
CTC cut-offs within 0.01-0.1% effectively dichotomized patients into low vs. high-risk of progression across clinical trials and routine practice, as well as in transplant-eligible and ineligible patients.
Patients with high CTC levels treated with anti-CD38 containing quadruplets had similar PFS to those with low CTC levels treated with triplets, indicating potential treatment strategy implications.
The 1% CTC cutoff identified 9% of patients with ultra-high-risk MM, providing a critical marker for risk stratification and individualized treatment planning.

Clinical relevance: Important but Not Practice Changing

While the findings are valuable and contribute to the understanding of risk stratification in multiple myeloma, they do not yet provide sufficient evidence to change clinical practice. Further research and validation are needed to establish CTCs as a standard prognostic tool in clinical settings.

Link to Abstract S199

Abstract Number: S201

PHASE 2 REGISTRATIONAL STUDY OF ANITOCABTAGENE AUTOLEUCEL FOR RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA (RRMM): UPDATED RESULTS FROM IMMAGINE-1

Presenter: Gurbakhash Kaur
Session: Treatment of relapsed and/or refractory multiple myeloma (RRMM)

Abstract Summary:

Anitocabtagene autoleucel (anito-cel) demonstrated a high overall response rate (ORR) of 97% in patients with relapsed and/or refractory multiple myeloma (RRMM), with a complete response/stringent complete response (CR/sCR) rate of 62%.
Among patients evaluable for minimal residual disease (MRD) testing, 93.1% achieved MRD negativity, with a median time to MRD negativity of 1 month.
At the 12-month milestone, the duration of response (DoR), progression-free survival (PFS), and overall survival (OS) rates were 75.6%, 78.5%, and 96.5%, respectively, with median DoR, PFS, and OS not yet reached.
The most common grade ≥3 treatment-emergent adverse events were cytopenias, including neutropenia (54%), anemia (22%), and thrombocytopenia (20%).
Cytokine release syndrome (CRS) was observed in 83% of patients, primarily grade 1, with no delayed or non-ICANS neurotoxicities reported, indicating a manageable safety profile.

Clinical relevance: Important but Not Practice Changing

While the results are promising and suggest that anitocabtagene autoleucel could become an important treatment option for RRMM, further studies, particularly Phase 3 trials, are needed to confirm these findings and establish its role in clinical practice. Therefore, the study is classified as important but not practice changing at this time.

Link to Abstract S201

Abstract Number: S202

LINVOSELTAMAB + CARFILZOMIB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: INITIAL RESULTS FROM THE LINKER-MM2 TRIAL

Presenter: Salomon Manier
Session: Treatment of relapsed and/or refractory multiple myeloma (RRMM)

Abstract Summary:

LINVOSELTAMAB plus carfilzomib achieved high objective response rates in relapsed/refractory multiple myeloma: 91% at DL1 (≥VGPR 91%) and 100% at DL1b (≥VGPR 80%), with median duration of response not reached at either dose level.
Progression-free survival at DL1 was 91% at 6 months and 73% at 12 months; no PFS events occurred at DL1b during the reported follow-up.
The safety profile was consistent with known effects of the individual agents; most common grade 3-4 treatment-emergent adverse events were neutropenia (61%), thrombocytopenia (39%), and infections (44%). Cytokine release syndrome occurred in 61% (no grade ≥3), and one case of grade 1 ICANS was reported.
Pharmacokinetic analysis showed that carfilzomib did not affect LINVOSELTAMAB concentrations.
Findings support further development of the combination, with ongoing enrollment at higher LINVOSELTAMAB doses.

Clinical relevance: Interesting but Limited Impact

In summary, while the high response rates and manageable safety profile are encouraging, the early-phase, small, uncontrolled nature of the study precludes any immediate clinical impact. The results support further investigation but do not yet alter the standard of care for relapsed/refractory multiple myeloma.

Link to Abstract S202

Abstract Number: S203

ISATUXIMAB SUBCUTANEOUS VIA AN ON-BODY DELIVERY SYSTEM VERSUS ISATUXIMAB INTRAVENOUS, PLUS POMALIDOMIDE AND DEXAMETHASONE, IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: THE RANDOMIZED PHASE 3 IRAKLIA STUDY

Presenter: Dr. Xavier Leleu
Session: Treatment of relapsed and/or refractory multiple myeloma (RRMM)

Abstract Summary:

The IRAKLIA trial demonstrated that isatuximab subcutaneous (Isa SC) via an on-body delivery system (OBDS) is non-inferior to intravenous isatuximab (Isa IV) in terms of overall response rate (ORR) and pharmacokinetics in relapsed/refractory multiple myeloma (RRMM), with ORRs of 71.1% for SC and 70.5% for IV.
Pharmacokinetic analysis showed a higher mean trough level for Isa SC (499 μg/mL) compared to Isa IV (340 μg/mL), with the geometric mean ratio supporting non-inferiority.
Grade ≥3 treatment-emergent adverse events were similar between groups, occurring in 81.7% of the SC arm and 76.1% of the IV arm, with low discontinuation rates (8.4% SC, 8.7% IV).
Injection site reactions were minimal in the SC arm, with only 4.2% of patients experiencing them, all of Grade 1-2 severity, and 99.9% of OBDS injections completed without interruption.
Isa SC OBDS showed fewer infusion reactions and higher patient satisfaction compared to Isa IV, supporting its potential to enhance patient experience and practice efficiency.

Clinical relevance: Important but Not Practice Changing

While the findings are valuable and suggest a potential improvement in patient experience and practice efficiency, they do not provide evidence of superior clinical outcomes over the current standard-of-care. Therefore, the study is classified as important but not practice changing.

Link to Abstract S203

Abstract Number: S204

DARATUMUMAB OR OBSERVATION FOR MINIMAL RESIDUAL DISEASE REAPPERANCE IN MULTIPLE MYELOMA: RESULTS FROM THE PREDATOR-MRD RANDOMIZED TRIAL

Presenter: Krzysztof Jamroziak
Session: Treatment of relapsed and/or refractory multiple myeloma (RRMM)

Abstract Summary:

Early intervention with daratumumab in multiple myeloma patients experiencing MRD relapse significantly delayed clinical progression, with a hazard ratio of 0.20 and a median event-free survival not reached in the daratumumab arm compared to 9.5 months in the observation arm (P = 0.0097).
MRD negativity was restored in 58.3% of patients treated with daratumumab within two months of treatment initiation, indicating its potential to reverse MRD relapse.
No deaths occurred during the study, and adverse events were predominantly grade 1-2, with infections and pain being the most common in the daratumumab arm (58% and 33%, respectively).
The study supports the use of daratumumab as an effective early intervention strategy for delaying progression and achieving MRD negativity in MM patients with MRD relapse.
Baseline characteristics were balanced between treatment arms, with a median follow-up of 17.9 months, ensuring robust comparative analysis.

Clinical relevance: Important but Not Practice Changing

Overall, while the study provides valuable insights into the potential benefits of early intervention with daratumumab for MRD relapse in multiple myeloma, the findings are not yet strong enough to change clinical practice. Larger, confirmatory phase 3 trials are needed to establish the efficacy and safety of this approach before it can be recommended as a new standard of care.

Link to Abstract S204

Abstract Number: S205

MINIMAL RESIDUAL DISEASE-DRIVEN STRATEGY FOLLOWING ISATUXIMAB-CARFILZOMIB-LENALIDOMIDE-DEXAMETHASONE INDUCTION IN TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA: PRIMARY ENDPOINTS OF THE PHASE 3 MIDAS TRIAL

Presenter: Aurore Perrot
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

In post-induction MRD-negative (10⁻⁵) NDMM patients, pre-maintenance MRD negativity at 10⁻⁶ was similar between IsaKRD consolidation (84%) and ASCT plus IsaKRD (86%), with no statistically significant difference (OR 1.17, 95% CI 0.64–2.76, p = 0.64).
Among MRD-positive (≥10⁻⁵) patients, pre-maintenance MRD negativity at 10⁻⁶ was 40% with single ASCT plus IsaKRD and 32% with tandem ASCT, also not statistically significant (OR 0.73, 95% CI 0.42–1.25, p = 0.31).
No new safety signals were observed during consolidation; disease progression and mortality rates were low across all arms.
Tandem ASCT did not significantly improve deep MRD negativity rates in MRD-positive patients after induction.
Long-term outcomes, including sustained MRD negativity and PFS, are pending with ongoing follow-up.

Clinical relevance: Important but Not Practice-Changing

In summary, this phase 3 trial provides important evidence that MRD-adapted strategies may allow for de-escalation of therapy in select NDMM patients, but definitive clinical benefit (in terms of PFS/OS) is not yet established. The results are hypothesis-generating and will inform future practice pending longer-term outcomes.

Link to Abstract S205

Abstract Number: S207

A RANDOMIZED, MULTI-CENTER STUDY OF CARFILZOMIB, LENALIDOMIDE AND DEXAMETHASONE (KRD) WITH OR WITHOUT DARATUMUMAB (D) FOR THE TREATMENT OF PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): THE ADVANCE CLINICAL TRIAL

Presenter: C. Ola Landgren
Session: Treatment of newly diagnosed multiple myeloma (NDMM)

Abstract Summary:

The addition of daratumumab to carfilzomib, lenalidomide, and dexamethasone (DKRd) significantly increased the MRD negativity rate to 59% compared to 36% with KRd alone, with an adjusted odds ratio of 2.5 (95% CI: 1.5-4.2; P<0.0007).
At a median follow-up of 32.7 months, progression-free survival (PFS) events were similar between the groups, with 86% of DKRd and 79% of KRd patients being progression-free and censored.
Adverse events were common, with hematologic AEs occurring in 15% of DKRd and 24% of KRd patients. Cardiac events were reported in 13% of DKRd and 16% of KRd patients, while infection rates were 61% and 53%, respectively.
Serious adverse events included pneumonia (3% DKRd vs 10% KRd) and acute kidney injury (1% DKRd vs 4% KRd), with no new safety signals identified.
These findings suggest that DKRd should be considered a new standard of care for NDMM patients receiving initial KRd-backbone therapy, pending further updates on EFS, PFS, and OS.

Clinical relevance: Important but Not Practice Changing

While the study presents promising results with a significant improvement in MRD negativity rates, the lack of mature survival data means it is not yet practice changing. The findings are important and suggest a potential future shift in treatment paradigms pending further data on long-term outcomes.

Link to Abstract S207

Abstract Number: S208

ANALYSIS OF SUSTAINED MRD NEGATIVITY IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA TREATED WITH CARFILZOMIB-LENALIDOMIDE-DEXAMETHASONE WITH OR WITHOUT ISATUXIMAB (PHASE III ISKIA TRIAL)

Presenter: Francesca Gay
Session: Treatment of newly diagnosed multiple myeloma (NDMM)

Abstract Summary:

The IsKia trial demonstrated that adding isatuximab to carfilzomib-lenalidomide-dexamethasone (Isa-KRd) significantly increased the rates of 10^-6 sustained MRD negativity in newly diagnosed multiple myeloma (NDMM) patients compared to KRd alone, with rates of 52% vs. 38% (OR 1.82; p=0.012) after light consolidation.
Isa-KRd showed a notable advantage in achieving 10^-6 1-year sustained MRD negativity across all subgroups, particularly in patients with ≥2 high-risk cytogenetic abnormalities, achieving rates of 62% vs. 20% (OR 6.3, 95% CI 1.11-35.66).
The safety profile of Isa-KRd was comparable to KRd, with similar rates of grade 3-4 hematologic and non-hematologic adverse events, and no significant increase in treatment-related discontinuations or deaths.
The trial supports the use of Isa-KRd as a more effective induction-consolidation regimen for NDMM, particularly in high-risk patients, without additional safety concerns.

Clinical relevance: Important but Not Practice Changing

While the study provides valuable insights into the potential benefits of adding isatuximab to the KRd regimen, particularly in achieving deeper MRD negativity, the lack of direct evidence linking these findings to improved long-term clinical outcomes means that the results are not yet strong enough to change current clinical practice. Further follow-up and additional studies are needed to confirm the impact on survival outcomes.

Link to Abstract S208

Abstract Number: S209

ISATUXIMAB, CARFILZOMIB, LENALIDOMIDE, AND DEXAMETHASONE (ISA-KRD) FOR HIGH-RISK (HR) NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): FIRST-TIME REPORT OF THE FULL COHORT OF TRANSPLANT-ELIGIBLE (TE) PATIENTS IN THE GMMG-CONCEPT TRIAL

Presenter: Lisa Leypoldt
Session: Treatment of newly diagnosed multiple myeloma (NDMM)

Abstract Summary:

The CONCEPT trial achieved its primary endpoint with a 73.2% MRD-negativity rate after consolidation in transplant-eligible (TE) patients with high-risk newly diagnosed multiple myeloma (NDMM), surpassing the null hypothesis of ≤50%.
Overall, 58.4% of patients reached MRD-negativity, with 86.8% achieving MRD-negativity at any time, and 64.8% and 40.6% maintaining MRD-negativity for ≥1 year and ≥2 years, respectively.
Median progression-free survival (PFS) for TE patients was 69.7 months, with overall survival (OS) not yet reached, indicating significant long-term benefits of the Isa-KRd regimen.
Carfilzomib administered once weekly resulted in fewer discontinuations (0.6%) compared to twice weekly (4.8%), though it led to more dose reductions (9.5% vs. 5.5%).
The trial supports Isa-KRd as a standard-of-care regimen for high-risk NDMM, demonstrating unprecedented MRD-negativity and sustained survival benefits in this challenging patient population.

Clinical relevance: Important but Not Practice Changing

While the results are promising and suggest potential improvements in outcomes for high-risk NDMM patients, the evidence from this Phase II trial is not yet sufficient to change clinical practice. Further validation in Phase III trials is necessary to confirm these findings and establish Isa-KRd as a new standard-of-care regimen.

Link to Abstract S209

Abstract Number: S284

PREDICTORS AND OUTCOMES FOR IMMUNE EFFECTOR CELL ASSOCIATED DELAYED NEUROTOXICITIES IN MULTIPLE MYELOMA PATIENTS RECEIVING CILTA-CEL: A REAL WORLD ANALYSIS FROM THREE US CENTERS

Presenter: Kenneth Jin Chang Lim
Session: Gene therapy, cellular immunotherapy and vaccination - Clinical

Abstract Summary:

In a cohort of 235 patients treated with cilta-cel, 9.7% developed delayed neurotoxicity, with 3.8% experiencing immune effector cell Parkinsonism (IEC-PKS) and 6.4% experiencing cranial and peripheral nerve palsies (IEC-NP).
Key risk factors for IEC-PKS included age >75 years, plasma cell burden >20%, involved free light chains ≥20mg/dL, ICANS, post-infusion ferritin ≥400mcg/L, and a post-infusion peak absolute lymphocyte count (ALC) of ≥3 x 10⁹/L, with peak ALC being the most significant predictor.
For IEC-NP, a post-infusion peak ALC of ≥3 x 10⁹/L was a significant risk factor, with an absolute risk of 30% for delayed neurotoxicity in patients with this ALC level.
Early intervention with systemic/oral steroids led to symptom resolution in 85% of IEC-NP cases, while cyclophosphamide treatment showed rapid symptom improvement in IEC-PKS cases.
Post-infusion peak ALC of ≥3 x 10⁹/L may serve as a predictive marker for toxicity and a potential threshold for primary prophylaxis in cilta-cel-treated patients.

Clinical relevance: Important but Not Practice Changing

While the study provides important insights into the management of cilta-cel-associated neurotoxicities, the findings are not yet strong enough to change clinical practice. Prospective studies are needed to validate these predictors and interventions before they can be routinely applied in clinical settings.

Link to Abstract S284

Abstract Number: S327

METHYLPHENIDATE ALLEVIATES FATIGUE IN HAEMATOLOGICAL CANCER: A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, CROSSOVER TRIAL - THE MICRO TRIAL

Presenter: Henrik Frederiksen
Session: Quality of Life and Health Economics

Abstract Summary:

Methylphenidate (MTP) significantly reduced fatigue in hematological cancer patients compared to placebo, with mean differences in fatigue scores favoring MTP: FACIT 5.9, VAS-F -1.3, and EORTC -14.2, all p<0.001.
Patients on MTP reported an increase of 0.7 more woken hours per day compared to those on placebo, indicating improved daily functioning.
Fatigue improvements with MTP exceeded minimal important difference thresholds on both FACIT and EORTC scales, suggesting clinically meaningful benefits.
Adverse events were generally mild, with grade 1 (43% vs 30%), grade 2 (21% vs 19%), and grade 3+ (3% vs 2%) for MTP vs placebo, with nausea and xerostomia being the most common.
The trial supports MTP as a potential treatment for alleviating severe fatigue in hematological cancer patients, with low short-term toxicity.

Clinical relevance: Important but Not Practice Changing

While the trial provides strong evidence that MTP can alleviate fatigue in hematological cancer patients, the lack of long-term data, comparison to other interventions, and the relatively small sample size suggest that these findings are important but not yet sufficient to change clinical practice. Further research is needed to confirm these results and explore the broader implications of MTP use in this patient population.

Link to Abstract S327

Abstract Number: S333

CLINICAL VALIDATION STUDY OF AN AI SYSTEM FOR BONE MARROW CELL CLASSIFICATION AND DYSPLASIA DETECTION

Presenter: David Bermejo-Peláez
Session: New developments in computational and AI-assisted hematology

Abstract Summary:

The AI system achieved a 92.5% overall agreement with hematologist consensus across 23 bone marrow cell types, with high accuracy in myeloid (95%), erythroid (99.9%), lymphoid (91.8%), monocytic (96.9%), blasts (90.9%), and plasma cell (97.3%) categories.
Dysplasia detection accuracy was 94% for erythroid and 94.6% for granulocytic lineages, with the AI's kappa agreement at 0.76, surpassing the inter-hematologist kappa of 0.52, indicating reduced diagnostic variability.
AI assistance reduced analysis time by 81%, decreasing the average time to classify 500 cells from 23.9 minutes (manual) to 4.5 minutes (AI-assisted) per sample.
The study validated the AI tool in a multicenter setting with 100 cases across various hematological conditions, demonstrating robustness across different staining methods.
This smartphone-integrated AI tool enhances diagnostic consistency and efficiency without requiring specialized imaging equipment, supporting broader AI adoption in hematology.

Clinical relevance: Important but Not Practice Changing

While the AI system offers significant improvements in workflow efficiency and diagnostic consistency, further studies are needed to establish its impact on clinical outcomes and its integration into routine practice. Therefore, it is classified as important but not practice changing at this stage.

Link to Abstract S333

Abstract Number: PF686

CD70/CD27 SIGNALING PROMOTES CLONAL PLASMA CELL EXPANSION IN MULTIPLE MYELOMA AND REPRESENTS A PROMISING THERAPEUTIC TARGET

Presenter: Maxime Boy
Session: Myeloma and other monoclonal gammopathies - Biology & translational research

Abstract Summary:

CD70 expression is significantly upregulated in relapsed and therapy-refractory multiple myeloma (MM), correlating with poor overall survival and high-risk cytogenetic features.
CD70/CD27 signaling promotes clonal plasma cell expansion via the MAPK/ERK pathway, contributing to MM progression.
Inhibition of CD70/CD27 signaling with monoclonal antibodies, such as cusatuzumab, effectively reduces myeloma cell proliferation and slows disease progression.
Cusatuzumab enhances NK cell activation and cytotoxicity against CD70-expressing myeloma cells, showing improved efficacy in vivo.
Combining CD70-targeting therapies with standard MM treatments, like bortezomib, daratumumab, or teclistamab, results in synergistic effects, suggesting CD70 as a promising immunotherapeutic target in MM.

Clinical relevance: Important but Not Practice Changing

While the study provides valuable insights into the role of CD70/CD27 signaling in MM and suggests potential therapeutic strategies, the evidence is not yet sufficient to change clinical practice. Further clinical trials are needed to validate these findings and determine their impact on patient outcomes.

Link to Abstract PF686

Abstract Number: PF691

DIFFERENTIATING BETWEEN MM-LIKE AND MGUS-LIKE SMOLDERING MYELOMA

Presenter: Anil Aktas Samur
Session: Myeloma and other monoclonal gammopathies - Biology & translational research

Abstract Summary:

Analysis of paired SMM and MM samples showed over 80% of driver events were present in both conditions, with 66% of patients having the same clones at both time points, indicating genomic pre-equipment for myeloma in progressor SMM.
Non-progressor SMM (NP-SMM) samples exhibited significantly less DNA damage, with reduced mutational load, fewer genome-wide focal deletions, and a lower genomic scar score compared to progressor SMM (P-SMM).
Mutations in NRAS, BRAF, FAM46C (TENT5C), and ATM were significantly more frequent in P-SMM, while MYC translocations were nearly exclusive to progressor patients, suggesting distinct genomic profiles between progressors and non-progressors.
A decision tree model using genomic features effectively identified low-risk SMM patients, achieving 91% sensitivity and 70% specificity in an independent validation cohort.
The study suggests that progressor SMM resembles MM, while non-progressor SMM is more MGUS-like, potentially impacting future diagnostic criteria and trial designs.

Clinical relevance: Important but Not Practice Changing

Overall, while the study provides valuable insights into the genomic landscape of SMM and its progression risk, further research and validation are needed before these findings can be translated into practice-changing strategies. The study highlights an important step towards personalized medicine in SMM but does not yet alter current clinical management.

Link to Abstract PF691

Abstract Number: PF713

MASS SPECTROMETRY ENABLES PRECISE MONITORING OF BISPECIFIC ANTIBODY THERAPY IN MULTIPLE MYELOMA

Presenter: Dr. M Teresa Cedena
Session: Myeloma and other monoclonal gammopathies - Biology & translational research

Abstract Summary:

Mass spectrometry (MS) effectively differentiates therapeutic bispecific antibodies from monoclonal proteins (MP) in multiple myeloma (MM), with observed mass-to-charge (m/z) values closely matching theoretical values, ensuring precise monitoring.
After three months of treatment with bispecific antibodies, 66% of patients achieved complete response (CR), 10% very good partial response (VGPR), and 24% partial response (PR), demonstrating significant efficacy.
MS showed superior sensitivity over immunofixation electrophoresis (IF), identifying MP in 5 cases where IF was negative, highlighting its enhanced diagnostic capability.
Measurable residual disease (MRD) was undetectable in all 19 patients assessed using next-generation flow (NGF), with only one patient experiencing relapse during a median follow-up of 12 months.
MS provides clinical value in MM by improving specificity in disease monitoring and optimizing patient management, with further follow-up needed to evaluate long-term response duration.

Clinical relevance: Important but Not Practice Changing

While the study provides valuable insights into the use of MS for monitoring bispecific antibody therapy in MM, the limited sample size, lack of long-term data, and absence of a control group mean that these findings, although promising, are not yet strong enough to change clinical practice. Further research is needed to confirm these results and explore their implications for patient care.

Link to Abstract PF713

Abstract Number: PF724

OUTCOME OF EARLY INTERVENTION AT MRD PROGRESSION IN MULTIPLE MYELOMA PATIENTS FOLLOWING AUTOLOGOUS STEM CELL TRANSPLANTATION: : A RETROSPECTIVE ANALYSIS

Presenter: Juan Li
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Early salvage intervention (ERI) at MRD progression (MRD-P) significantly extends overall survival (OS) compared to treatment initiated after biochemical or clinical progression, with ERI patients showing a median OS of 44.5 months versus not reached in the PD group (P = 0.048).
ERI is associated with a significantly longer time to progression, with a median time to progressive disease of 34.8 months compared to 5.9 months for those who waited for clinical or biochemical progression (P = 0.012).
The cumulative MRD negativity rate is significantly higher in the ERI group, with 77.8% achieving MRD negativity, compared to lower rates in the PD group (P < 0.001).
Risk factors for achieving second MRD negativity include ERI after MRD relapse (HR 0.07, 95% CI 0.01-0.36, P = 0.001) and a low proportion of abnormal plasma cells at treatment (HR 0.29, 95% CI 0.09-0.97, P = 0.045).
High-risk cytogenetics, such as double-hit, are associated with a lower likelihood of achieving MRD negativity, highlighting the need for tailored treatment strategies.

Clinical relevance: Important but Not Practice Changing

In summary, while the findings are important and suggest a potential benefit of early intervention at MRD-P, the evidence is not yet strong enough to warrant a change in clinical practice. Further research, particularly prospective RCTs, is needed to confirm these results and establish ERI as a standard treatment strategy in multiple myeloma.

Link to Abstract PF724

Abstract Number: PF726

DREAMM-8: MINIMAL RESIDUAL DISEASE NEGATIVITY IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA TREATED WITH BELANTAMAB MAFODOTIN, POMALIDOMIDE, AND DEXAMETHASONE VS STANDARD-OF-CARE REGIMEN

Presenter: Prof. Dr. Meletios Dimopoulos
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

BPd (belantamab mafodotin, pomalidomide, dexamethasone) resulted in a 5-fold higher rate of CR-based MRD negativity compared to PVd (pomalidomide, bortezomib, dexamethasone): 24% vs 5%.
MRD negativity was strongly associated with improved progression-free survival (PFS) and overall survival (OS); CR-based MRD neg patients had a significantly lower risk of progression or death (PFS HR 0.14; 95% CI, 0.06-0.32) and lower risk of death (OS HR 0.18; 95% CI, 0.07-0.49).
Among patients without CR-based MRD negativity, BPd provided a clinically meaningful PFS benefit over PVd (median PFS: 19.6 vs 10.2 months; HR 0.67; 95% CI, 0.47-0.94).
Depth of response, as measured by MRD negativity, is a key predictor of long-term outcomes in RRMM, and BPd achieves greater depth of response than PVd.

Clinical relevance: Important but Not Practice-Changing

In summary, DREAMM-8 provides meaningful evidence that BPd improves depth of response and PFS over PVd in RRMM, but the lack of mature OS data and detailed safety outcomes precludes immediate changes to standard practice. The results are important and may inform future guidelines pending further data and regulatory review.

Link to Abstract PF726

Abstract Number: PF727

ISA-VRD IMPROVES OUTCOMES IN HIGH-RISK (HR) NEWLY DIAGNOSED TRANSPLANT-INELIGIBLE MULTIPLE MYELOMA (NDMM TI) USING THE IMS/IMWG CONSENSUS HR DEFINITION: RESULTS FROM THE BENEFIT PHASE 3 TRIAL (IFM 2020-05)

Presenter: Jill Corre
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

The Isa-VRd regimen demonstrated superior MRD negativity rates compared to Isa-Rd in high-risk (HR) newly diagnosed transplant-ineligible multiple myeloma (NDMM TI) patients, with 50% achieving MRD negativity at 18 months versus 27% for Isa-Rd (OR 2.75, 95%CI, 1 to 7.5).
Sustained MRD negativity was significantly higher in the Isa-VRd group at 34% compared to 16% in the Isa-Rd group for the entire cohort (OR 2.73, 95%CI, 1.52 to 4.88, p=0.0007).
In HR patients, sustained MRD negativity rates were 31% for Isa-VRd versus 13% for Isa-Rd, although the difference was not statistically significant (OR 2.91, 95%CI: 0.84 to 10.6, p=0.091).
The safety profile was comparable between Isa-VRd and Isa-Rd in HR patients, indicating no additional safety concerns with the quadruplet regimen.
These findings support Isa-VRd as the new standard of care for NDMM TI patients aged 65 to 79, offering improved outcomes over the triplet-based regimen.

Clinical relevance: Important but Not Practice Changing

Overall, the study provides valuable insights into the potential benefits of the Isa-VRd regimen for high-risk NDMM TI patients, but the absence of mature survival data and the need for further validation in broader clinical settings suggest that these findings are important but not yet practice changing.

Link to Abstract PF727

Abstract Number: PF728

UPDATED RESULTS FROM PHASE 3 DREAMM-8 STUDY OF BELANTAMAB MAFODOTIN PLUS POMALIDOMIDE AND DEXAMETHASONE VS POMALIDOMIDE PLUS BORTEZOMIB AND DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA

Presenter: Prof. Dr. Meletios Dimopoulos
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Belantamab mafodotin plus pomalidomide and dexamethasone (BPd) demonstrated a significant progression-free survival (PFS) advantage over pomalidomide plus bortezomib and dexamethasone (PVd) in relapsed/refractory multiple myeloma (RRMM), with a hazard ratio (HR) of 0.49 and median PFS of 32.6 months versus 12.5 months for PVd.
The 18-month PFS rate was 63% for BPd compared to 41% for PVd, indicating sustained efficacy over time.
PFS benefits were consistent across subgroups, including patients with high-risk cytogenetics, lenalidomide-refractory, and anti-CD38-refractory disease, as well as those with one or more prior lines of therapy.
Updated safety results were consistent with previous analyses, with no new safety concerns, reinforcing the safety profile of BPd.
These findings support BPd as a potential standard-of-care option for patients with RRMM, particularly those with refractory disease profiles.

Clinical relevance: Important but Not Practice Changing

While the DREAMM-8 study provides valuable insights and demonstrates a significant PFS benefit for the BPd regimen, the absence of OS data and the need for further validation in broader clinical settings suggest that these findings are important but not yet practice changing. Further studies and longer follow-up are needed to confirm these results and potentially alter clinical practice.

Link to Abstract PF728

Abstract Number: PF729

ISATUXIMAB, BORTEZOMIB, LENALIDOMIDE, AND DEXAMETHASONE (ISA-VRD) IN NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): OUTCOMES IN PATIENTS WITH 1Q21+ STATUS IN THE PHASE 3 IMROZ STUDY

Presenter: Prof. Dr. Meletios Dimopoulos
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

In the IMROZ study, Isa-VRd significantly improved progression-free survival (PFS) compared to VRd in patients with 1q21+ status, including those with isolated 1q21+ and those with high-risk chromosomal abnormalities (HRCAs).
Patients treated with Isa-VRd achieved higher rates of complete response (CR) and minimal residual disease negativity (MRD-) compared to those receiving VRd, with sustained MRD- for ≥12 months.
The efficacy of Isa-VRd was consistent across subgroups, including those with gain(1q21) and amp(1q21), although specific data for these subgroups will be presented separately.
The findings align with previous studies using Isa-pomalidomide-dexamethasone and Isa-carfilzomib-dexamethasone, reinforcing Isa-VRd's role in improving outcomes for NDMM patients with 1q21+ status.
Overall, Isa-VRd offers a significant therapeutic advantage in transplant-ineligible NDMM patients with 1q21+ status, supporting its use as a preferred treatment regimen in this population.

Clinical relevance: Important but Not Practice Changing

While the study provides valuable insights and suggests a potential improvement in outcomes for a specific subgroup of NDMM patients, the findings are not yet strong enough to change practice universally. Further validation in broader populations and consideration of cost-effectiveness and feasibility are needed before this regimen can be recommended as a new standard of care.

Link to Abstract PF729

Abstract Number: PF730

CHALLENGING THE CONCEPT OF FUNCTIONAL HIGH-RISK MYELOMA THROUGH ADVANCED TRANSCRIPTIONAL AND GENETIC PROFILING.

Presenter: Sina A Beer
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

In a cohort of 135 transplant-eligible newly diagnosed multiple myeloma (NDMM) patients, 18.5% experienced early relapse (ER) despite comprehensive molecular profiling.
Among the ER group, 56% were identified as high-risk by IMWG criteria, with 32% also classified as high-risk by gene expression profiling (GEP), highlighting the utility of combined diagnostic approaches.
Only 8% of patients with ER had no high-risk markers, suggesting that functional high-risk multiple myeloma (HRMM) is rare when advanced profiling is applied.
Survival analysis showed significantly worse outcomes for patients with both IMWG-HR and GEP-HR, with a hazard ratio of 29.2 for overall survival compared to standard risk, underscoring the prognostic value of combined profiling.
The study advocates for improved access to advanced diagnostic technologies, as combined GEP and IMWG profiling can refine prognostication and enable stratified treatment approaches for multiple myeloma patients.

Clinical relevance: Important but Not Practice Changing

Overall, while the study provides valuable insights into the genetic and transcriptional underpinnings of high-risk multiple myeloma and suggests a path toward more personalized treatment strategies, it does not yet provide evidence strong enough to change current clinical practice. Further research and validation in larger, diverse cohorts are needed to establish the clinical utility of these findings.

Link to Abstract PF730

Abstract Number: PF731

DARATUMUMAB, BORTEZOMIB, LENALIDOMIDE AND DEXAMETHASONE (DVRD) VS VRD IN TRANSPLANT-INELIGIBLE/TRANSPLANT-DEFERRED NEWLY DIAGNOSED MULTIPLE MYELOMA: PHASE 3 CEPHEUS TRIAL CYTOGENETIC SUBGROUP ANALYSIS

Presenter: Mr. Nizar J Bahlis
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

DVRd significantly increased MRD-negativity rates compared to VRd in standard-risk (64% vs 38%; P<0.0001) and revised standard-risk (68% vs 38%; P<0.0001) transplant-ineligible/deferred NDMM patients.
≥1-year sustained MRD-negativity rates were higher with DVRd in standard-risk (51% vs 26%; P<0.0001) and revised standard-risk (54% vs 24%; P<0.0001) groups.
Progression-free survival (PFS) was improved with DVRd vs VRd in standard-risk and revised standard-risk patients; PFS was similar between arms in high-risk and revised high-risk subgroups.
In high-risk and revised high-risk patients, MRD-negativity and PFS outcomes were comparable between DVRd and VRd, with both arms trending lower than standard-risk groups; the study was underpowered for high-risk subgroup analysis.
Data support DVRd as a preferred regimen for TIE or TD NDMM, particularly in standard-risk patients, regardless of cytogenetic risk status.

Clinical relevance: Important but Not Practice-Changing

In summary, this study provides important, high-quality evidence supporting DVRd over VRd in standard-risk, transplant-ineligible/deferred NDMM, but does not justify a universal change in practice, particularly for high-risk cytogenetic subgroups. The findings are meaningful and reinforce current trends, but are not practice-changing for the entire NDMM population.

Link to Abstract PF731

Abstract Number: PF733

EXTENDED DOSING SCHEDULE OF BELANTAMAB MAFODOTIN IN COMBINATION WITH DARATUMUMAB, LENALIDOMIDE AND DEXAMETHASONE IN PATIENTS WITH NEWLY DIAGNOSED MULTIPLE MYELOMA: THE PHASE 1/2 BELADRD STUDY

Presenter: Prof. Evangelos Terpos
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

BelaDRd demonstrated a high overall response rate (ORR) of 91.7% in Part 1 and 90% in Part 2, with rapid median time to first response of approximately 1 month, indicating significant clinical activity in newly diagnosed multiple myeloma (NDMM) patients.
Progression-free survival (PFS) rates were impressive, with 12/24-months PFS rates at 83.3% and 100% for Part 1 cohorts, and a 6-month PFS rate of 100% in Part 2, suggesting sustained efficacy.
Ocular adverse events (OAEs) were managed effectively with an extended dosing schedule, resulting in a low frequency of ≥Grade 3 OAEs, which resolved rapidly, maintaining tolerability.
The study population included a significant proportion of intermediate-fit/frail patients, yet no progressive disease was observed, highlighting the regimen's potential in unfit populations.
The promising PFS and manageable safety profile suggest that a phase 3 study comparing BelaDRd to other novel quadruplet combinations for NDMM patients may be warranted.

Clinical relevance: Important but Not Practice Changing

Overall, while the study presents promising early-phase data, the findings are not yet strong enough to change clinical practice. Further investigation in larger, randomized trials is necessary to confirm the benefits and safety of the BelaDRd regimen compared to current standards.

Link to Abstract PF733

Abstract Number: PF737

IBERDOMIDE, BORTEZOMIB, AND DEXAMETHASONE (IBERVD) IN TRANSPLANT-INELIGIBLE (TNE) NEWLY DIAGNOSED MULTIPLE MYELOMA (NDMM): UPDATED RESULTS FROM THE CC-220-MM-001 TRIAL

Presenter: Darrell White
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

IberVd (iberdomide, bortezomib, dexamethasone) achieved a 100% overall response rate in evaluable transplant-ineligible NDMM patients, with ≥ complete response (CR) rate increasing from 56.3% to 75.0% after 13–25 months of follow-up.
MRD negativity at 10^-5 was observed in 50% of patients, all of whom achieved at least CR, indicating deep and durable responses.
Median time to response was rapid at 0.7 months, and median duration of response was not reached, with some patients deepening response after 1 year of treatment.
Grade 3/4 treatment-emergent adverse events occurred in 82.4% of patients, primarily infections (47.1%) and neutropenia (29.4%), but were manageable with dose modifications and supportive care.
No new safety signals emerged with longer follow-up, supporting further evaluation of IberVd in the frontline setting for transplant-ineligible NDMM.

Clinical relevance: Interesting but Limited Impact

In summary, while the data are intriguing and support continued development of IberVd, the current evidence is insufficient to influence clinical care or alter standard treatment paradigms for transplant-ineligible NDMM at this stage.

Link to Abstract PF737

Abstract Number: PF738

SERUM FREE LIGHT CHAIN DIFFERENCE (DSFLC) AS A ROBUST PREDICTOR FOR MULTIPARAMETER FLOW CYTOMETRY-BASED MINIMAL RESIDUAL DISEASE POSITIVITY IN MULTIPLE MYELOMA: A COHORT STUDY GUIDING OPTIMAL MONITORING STRATEGIES

Presenter: Fan Zhang
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

dFLC demonstrated strong predictive performance for MFC-MRD positivity in multiple myeloma, with an AUC of 0.833 in the training cohort and 0.880 in the validation cohort, indicating high accuracy.
The optimal dFLC cutoff was identified at 11.80 mg/L, achieving a sensitivity of 75.5% and specificity of 75.9% in the training cohort, and 71.7% sensitivity and 87.3% specificity in the validation cohort.
Pooled analysis confirmed the robustness of dFLC as a predictor, with an AUC of 0.837, maintaining sensitivity and specificity at 74.3% and 79.3%, respectively.
Subgroup analyses showed consistent predictive power (AUC >0.80) across various patient strata, including ASCT status, genetic risk, ISS stage, and relapsed/refractory disease.
dFLC is a cost-effective biomarker that can enhance MRD monitoring by reducing unnecessary invasive procedures, supporting biomarker-driven MRD surveillance and tailored therapeutic strategies in MM.

Clinical relevance: Important but Not Practice Changing

Overall, while the study presents valuable insights into the use of dFLC as a predictor for MFC-MRD positivity, the findings are not yet strong enough to alter current clinical practice. Further research, including prospective studies demonstrating improved patient outcomes, would be necessary to elevate these findings to a practice-changing level.

Link to Abstract PF738

Abstract Number: PF739

DREAMM-7 STUDY OF BELANTAMAB MAFODOTIN + BORTEZOMIB + DEXAMETHASONE VS DARATUMUMAB + BORTEZOMIB + DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: A HIGH-RISK CYTOGENETIC SUBGROUP ANALYSIS

Presenter: Dr. María-Victoria Mateos
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

BVd (belantamab mafodotin + bortezomib + dexamethasone) significantly improved median progression-free survival (PFS) in RRMM patients with ≥1 high-risk cytogenetic abnormality (HRCA): 33.2 months vs 11.1 months for DVd (daratumumab + bortezomib + dexamethasone), HR 0.40 (95% CI, 0.27-0.59).
18-month PFS rates were higher with BVd (61%) compared to DVd (38%) in the HRCA subgroup.
BVd demonstrated superior PFS across all analyzed HRCA subgroups: t(4;14) HR 0.36, 17p13del HR 0.25, amp1q HR 0.48.
Overall response rate in patients with ≥1 HRCA was higher with BVd (81%) than DVd (69%), with a greater proportion achieving complete response or better.
Findings support BVd as a potential standard-of-care regimen for RRMM patients with high-risk cytogenetics, addressing a significant unmet clinical need.

Clinical relevance: Important but Not Practice-Changing

In summary, this analysis provides strong evidence that BVd may be a superior option for RRMM patients with HRCAs, but the findings—while important—are not yet sufficient to mandate a change in clinical practice. They should inform ongoing research, guideline discussions, and shared decision-making in high-risk RRMM.

Link to Abstract PF739

Abstract Number: PF741

DREAMM-8 STUDY OF BELANTAMAB MAFODOTIN + POMALIDOMIDE + DEXAMETHASONE VS POMALIDOMIDE + BORTEZOMIB + DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: A HIGH-RISK CYTOGENETIC SUBGROUP ANALYSIS

Presenter: Prof. Dr. Meletios Dimopoulos
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

BPd (belantamab mafodotin + pomalidomide + dexamethasone) significantly improved median progression-free survival (PFS) in RRMM patients with high-risk cytogenetic abnormalities (HRCAs): 21.1 months (95% CI, 13.5-NR) vs 9.2 months (95% CI, 6.5-14.8) for PVd (pomalidomide + bortezomib + dexamethasone), HR 0.58 (95% CI, 0.36-0.95).
18-month PFS rates were higher with BPd (53%) compared to PVd (33%) in the HRCA subgroup.
BPd demonstrated a higher overall response rate (ORR) in patients with ≥1 HRCA: 76% (95% CI, 64.6%-85.9%) vs 65% (95% CI, 51.6%-76.9%) for PVd, with more patients achieving ≥ complete response.
PFS and response benefits with BPd were consistent across individual HRCA subgroups, including del(17p13) and amp1q.
Findings support BPd as a potential standard-of-care regimen for RRMM patients with high-risk cytogenetic features.

Clinical relevance: Important but Not Practice-Changing

In summary, this analysis provides important evidence supporting BPd as a potentially superior regimen for RRMM patients with high-risk cytogenetics, but further data and broader validation are required before it can be considered practice-changing.

Link to Abstract PF741

Abstract Number: PF742

FIRST RESULTS FROM REALITAL: A EUROPEAN MULTI-COUNTRY OBSERVATIONAL RETROSPECTIVE STUDY OF TALQUETAMAB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA OUTSIDE OF CLINICAL TRIALS

Presenter: K. Martin Kortüm
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

The REALiTAL study, a retrospective observational study, reported an overall response rate (ORR) of 66.7% in patients with relapsed/refractory multiple myeloma treated with talquetamab, with 57% achieving ≥VGPR.
Median progression-free survival (PFS) was 8.18 months, and median overall survival (OS) was 25.3 months, indicating significant efficacy in a heavily pre-treated population.
Patients achieving ≥VGPR had a longer median duration of response (DoR) of 13.4 months, with median PFS and OS of 18.2 and 25.26 months, respectively, highlighting the benefit of deep responses.
Common adverse events included skin/nail toxicity (67.7%), oral toxicity (66.7%), cytokine release syndrome (CRS) (55.9%), and infections (47.3%), with 6.5% of patients discontinuing treatment due to adverse events.
The study's outcomes are consistent with the MonumenTAL-1 trial, reinforcing talquetamab's activity and tolerability in a real-world, hard-to-treat patient population.

Clinical relevance: Important but Not Practice Changing

While the REALiTAL study offers important real-world data that corroborates the efficacy and safety of talquetamab in a difficult-to-treat population, it does not present new evidence that would alter existing clinical practice. Therefore, it is classified as important but not practice changing.

Link to Abstract PF742

Abstract Number: PF743

IMPACT OF SELINEXOR DOSE REDUCTIONS ON SELINEXOR, BORTEZOMIB, DEXAMETHASONE (SVD) OUTCOMES IN PATIENTS (PTS) WITH LENALIDOMIDE (LEN)-REFRACTORY MULTIPLE MYELOMA (MM): BOSTON TRIAL SUBGROUP ANALYSIS

Presenter: Sosana Delimpasi
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Selinexor dose reductions in LEN-refractory multiple myeloma patients led to higher overall response rates (ORR) of 74% compared to 56% in those without dose reductions.
Patients with dose reductions experienced a longer median duration of response (DOR) of 15.3 months versus 4.2 months for those without reductions.
Progression-free survival (PFS) was extended to 13.9 months in patients with dose reductions, compared to 5.1 months in those without.
Quality of life (QOL) scores improved more significantly in patients with dose reductions, with a mean best change from baseline of 10.4 versus 3.7.
Gastrointestinal treatment-related adverse events (TRAEs) such as nausea, fatigue, decreased appetite, and vomiting were reduced following selinexor dose reductions.

Clinical relevance: Important but Not Practice Changing

Overall, while the findings provide valuable insights into optimizing selinexor dosing for LEN-refractory patients, they do not yet warrant a change in clinical practice. Further research with larger sample sizes and prospective validation is needed to confirm these results and potentially influence treatment guidelines.

Link to Abstract PF743

Abstract Number: PF744

TO TREAT OR NOT? A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED STUDIES ON SMOLDERING MULTIPLE MYELOMA

Presenter: Dr. Ioannis Ntanasis-Stathopoulos
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Early treatment in smoldering multiple myeloma (sMM) significantly reduces the risk of disease progression or death by 60% compared to observation, with a hazard ratio (HR) of 0.40 (95% CI: 0.29-0.55).
In high-risk sMM patients, treatment further decreases the risk of progression or death by 66% (HR=0.34, 95% CI: 0.21-0.56) compared to observation.
Time-to-progression (TTP) analysis shows a 58% reduced risk of progression to symptomatic multiple myeloma for treated patients (HR=0.42, 95% CI: 0.29-0.61).
Overall survival (OS) outcomes indicate a 45% lower risk of death for patients receiving treatment versus observation (HR=0.55, 95% CI: 0.37-0.82).
Treatment-related serious adverse events are 3.5 times more likely in the treatment group (OR=3.53, 95% CI: 1.14-10.91), necessitating careful monitoring of toxicities.

Clinical relevance: Important but Not Practice Changing

While the meta-analysis provides valuable insights into the potential benefits of early treatment for high-risk sMM patients, the increased risk of adverse events and the need for careful patient selection suggest that these findings are important but not yet strong enough to change current clinical practice. Further research is needed to refine patient selection criteria and optimize treatment regimens to balance efficacy and safety.

Link to Abstract PF744

Abstract Number: PF745

HIGHER USE OF HDT/ASCT IN FIRST-LINE LEADS TO SUPERIOR SURVIVAL IN MULTIPLE MYELOMA PATIENTS AGED 66-70: REAL-WORLD EVIDENCE FROM THE NETHERLANDS

Presenter: Koen Klomberg
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

In multiple myeloma patients aged 66-70, those receiving HDT/ASCT had a 5-year OS of 74%, compared to 44% for those without, indicating a significant survival advantage.
Regional analysis showed a median OS of 87 months in high-utilization areas versus 62 months in low-utilization areas, highlighting the impact of HDT/ASCT adoption rates on survival.
Outcomes for patients aged 66-70 receiving HDT/ASCT were comparable to those of younger patients aged 18-65, suggesting similar benefits across these age groups.
No significant regional OS differences were observed in patients aged 18-65 or those over 70, underscoring that survival differences in the 66-70 age group are likely due to local HDT/ASCT implementation policies.
The study supports increased HDT/ASCT utilization in patients aged 66-70, given the substantial survival benefits observed in real-world settings.

Clinical relevance: Important but Not Practice Changing

Although the study provides compelling real-world evidence supporting the survival benefits of HDT/ASCT in patients aged 66-70, it does not introduce a novel treatment or mechanism that would immediately change clinical practice. Instead, it reinforces the importance of expanding current treatment strategies to older, fit patients, which is an important consideration but not a practice-changing revelation.

Link to Abstract PF745

Abstract Number: PF746

RISK FACTORS AND MODES OF PROGRESSION IN SOLITARY BONE PLASMACYTOMA WITH OR WITHOUT MINIMAL MARROW INVOLVEMENT

Presenter: Kenneth Jin Chang Lim
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

SBP and SBPmm, though treated similarly, exhibit distinct outcomes; SBPmm patients have a significantly higher risk of progression to multiple myeloma (MM).
In the SBP cohort, tumor size >5cm and abnormal free light chain (FLC) ratio were significant predictors of progression, with tumor size remaining significant in multivariate analysis (aHR 2.3).
SBPmm patients with del(17p) had a median time to progression (TTP) of 6 months, with 100% progressing within 2 years, highlighting the aggressive nature of this cytogenetic abnormality.
SBPmm patients with +1q abnormalities also showed high progression rates, with 78% progressing within 2 years, suggesting a need for more aggressive treatment strategies.
The findings suggest that SBPmm patients, particularly those with high-risk cytogenetic features, may benefit from the early incorporation of systemic therapy to mitigate progression risks.

Clinical relevance: Important but Not Practice Changing

Overall, the findings provide valuable insights into the risk factors and progression patterns of SBP and SBPmm, highlighting the need for further research into systemic therapy for high-risk patients. However, the evidence is not yet strong enough to warrant a change in clinical practice.

Link to Abstract PF746

Abstract Number: PF747

TALQUETAMAB IMMUNOGENICITY AND IMPACT ON EXPOSURE, EFFICACY, AND SAFETY: ANALYSES FROM PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA IN MONUMENTAL-1

Presenter: Indrajeet Singh
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Treatment-emergent antidrug antibodies (ADAs) and neutralizing antibodies (NAbs) were observed in 36% and 18% of patients with RRMM treated with talquetamab at recommended phase 2 doses, respectively.
The presence of ADAs and NAbs had no apparent impact on talquetamab serum concentration, pharmacokinetics, efficacy, or safety.
Overall response rates (ORR) were high in both ADA-positive (92% QW, 90% Q2W) and NAb-positive (96% QW, 100% Q2W) patients, and were not inferior to ADA-negative or NAb-negative patients.
Median time to first response was similar between ADA-positive and ADA-negative patients, and the onset of treatment-induced ADAs occurred well after initial response, indicating no causal impact on efficacy.
No major differences in adverse event incidence were observed between ADA/NAb-positive and ADA/NAb-negative groups.

Clinical relevance: Important but Not Practice-Changing

In summary, this study provides important reassurance that immunogenicity does not compromise the clinical utility of talquetamab in RRMM, but the results are not practice-changing as they do not alter current treatment paradigms or require new clinical actions.

Link to Abstract PF747

Abstract Number: PF753

ETOPOSIDE+CYTARABINE+PEGFILGRASTIM VS CYCLOPHOSPHAMIDE+GRANULOCYTE COLONY-STIMULATING FACTOR FOR STEM-CELL MOBILIZATION IN PATIENTS WITH MULTIPLE MYELOMA: A PHASE III TRIAL

Presenter: Peipei Ye
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

The EAP regimen (etoposide, cytarabine, pegfilgrastim) significantly outperformed the CG regimen (cyclophosphamide, G-CSF) in achieving optimal CD34⁺ cell collection in a single apheresis session, with 86.2% versus 35.7% of patients reaching the target (p=0.001).
All patients in the EAP group achieved the minimum target yield of ≥2×10⁶ CD34⁺ cells/kg, compared to 71.4% in the CG group, with fewer apheresis sessions required (average 1.2 vs. 1.7 sessions, p=0.003).
The median cumulative CD34⁺ cell yield was significantly higher in the EAP group (12.4 ×10⁶/kg) compared to the CG group (4.8 ×10⁶/kg, p<0.0001).
Both regimens had manageable safety profiles, with thrombocytopenia more common in the EAP group and neutropenia/infection in the CG group.
The low use of plerixafor in the EAP group suggests its potential as a first-line mobilization strategy for MM patients, particularly those unable to use plerixafor.

Clinical relevance: Important but Not Practice Changing

While the study presents promising results that could influence future mobilization strategies in multiple myeloma, the limited sample size and the need for further validation mean that these findings are important but not yet practice changing. Larger studies are needed to confirm these results and assess long-term outcomes before widespread adoption into clinical practice.

Link to Abstract PF753

Abstract Number: PF755

DEVELOPMENT AND VALIDATION OF A MULTIPLE MYELOMA-SPECIFIC COMORBIDITY INDEX FROM A KOREAN NATIONWIDE COHORT: CAREMM-2108

Presenter: Sung-Soo Park
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

The Multiple Myeloma-Specific Comorbidity Index (MM-CI) was developed using a large Korean cohort and validated with multicenter data, identifying key predictors of overall survival, including male sex, age, congestive heart failure, cerebrovascular disease, hepatic disease, and cancer.
The MM-CI stratifies patients into low, intermediate, and high-risk groups with median overall survival of 72.5, 39.6, and 20.3 months, respectively, demonstrating its effectiveness in survival prediction.
The MM-CI outperformed the age-adjusted Charlson Comorbidity Index (AUC: 0.644 vs. 0.625) and the concise age-adjusted CCI used in IMWG frailty scores (AUC: 0.562), indicating superior predictive accuracy.
The prognostic value of the MM-CI was consistent across different ECOG performance statuses, R2-ISS stages, and frontline treatment types, highlighting its robustness and applicability in clinical settings.
The study concludes that the MM-CI is a simple yet accurate tool for predicting survival outcomes in multiple myeloma patients, offering an improvement over existing frailty models.

Clinical relevance: Important but Not Practice Changing

Overall, while the MM-CI provides an improved method for assessing comorbidities in multiple myeloma patients, its current application is more prognostic than therapeutic, and further studies are needed to establish its role in clinical practice.

Link to Abstract PF755

Abstract Number: PF759

BASELINE OCULAR CONDITIONS AND INCIDENCE OF OCULAR EVENTS IN PATIENTS (PTS) WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA (RRMM) FROM THE DREAMM-7 AND DREAMM-8 TRIALS OF BELANTAMAB MAFODOTIN (BELAMAF)

Presenter: Dimopoulos Meletios
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Belantamab mafodotin (belamaf) combinations in DREAMM-7 and DREAMM-8 demonstrated significant progression-free survival benefits over standard of care in relapsed/refractory multiple myeloma; overall survival benefit was significant for BVd (DREAMM-7) and trending for BPd (DREAMM-8).
Baseline ocular conditions were present in 62% of patients, most commonly cataract (50%), keratopathy (14%), and dry eye (14%).
The incidence of treatment-emergent ocular adverse events (TE oAEs), corneal exam findings, and BCVA worsening was similar between patients with and without baseline ocular conditions across both trials.
Most ocular events were effectively managed with protocol-defined dose modifications, and the majority resolved or improved during the study.
Baseline ocular conditions did not increase the risk of ocular events with belamaf-based therapy, supporting the inclusion of patients with pre-existing ocular comorbidities.

Clinical relevance: Important but Not Practice-Changing

In summary, this analysis provides important reassurance regarding the safety of belamaf in patients with baseline ocular conditions, but it does not alter the overall risk profile or current clinical practice. The findings are relevant for refining patient selection and management but are not practice-changing.

Link to Abstract PF759

Abstract Number: PF762

EXPOSURE-RESPONSE ANALYSES OF VARIOUS EFFICACY AND SAFETY ENDPOINTS IN SUPPORT OF REGISTRATIONAL DOSE SELECTION OF LINVOSELTAMAB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA

Presenter: Swathi Namburi
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

The odds ratio for objective response rate (ORR) was 4.37 times higher for patients receiving 200 mg compared to 50 mg of linvoseltamab, indicating a significant efficacy advantage at the higher dose.
Time-to-event multivariate analysis showed a 39.5% reduction in risk of disease progression or death (HR 0.605) and a 30.6% reduction in risk of death (HR 0.694) for the 200 mg dose, supporting its use for improved progression-free survival (PFS) and overall survival (OS).
Efficacy was consistent across high-risk subgroups, with better outcomes linked to baseline markers of lower disease burden and better overall health, such as higher red blood cell levels and lower soluble BCMA, serum M protein, and lactate dehydrogenase levels.
Safety analyses indicated no increase in Grade ≥3 infections at the 200 mg dose, and a decrease in such infections over time, suggesting improved disease control and patient health.
The exposure-response analysis supports the 200 mg dose of linvoseltamab for relapsed/refractory multiple myeloma, highlighting dose-related improvements in both efficacy and safety.

Clinical relevance: Important but Not Practice Changing

While the study provides valuable insights into dose optimization and the potential benefits of linvoseltamab in RRMM, the evidence is not yet strong enough to change clinical practice. Further research, including larger and longer-term studies, is necessary to confirm these findings and establish linvoseltamab's role in the treatment landscape.

Link to Abstract PF762

Abstract Number: PF765

SURVIVAL BENEFIT OF CILTACABTAGENE AUTOLEUCEL IN SECOND-LINE COMPARED WITH LATER-LINE TREATMENT OF LENALIDOMIDE-REFRACTORY MULTIPLE MYELOMA: UPDATED TREATMENT POSITIONING MODEL ANALYSIS

Presenter: Dr. Roberto Mina
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Using ciltacabtagene autoleucel (cilta-cel) in the second line (2L) of treatment for lenalidomide-refractory multiple myeloma (MM) resulted in a median overall survival (OS) of 12.8 years, compared to 9.3 years when used in third line or later (3L+).
The predicted OS rates at 5 and 10 years were significantly higher when cilta-cel was used in 2L, at 75.5% and 57.2%, respectively, compared to 61.6% and 48.6% when used in 3L+.
The OS rate difference between using cilta-cel in 2L versus 3L+ was 14.0% at 5 years and 8.6% at 10 years, indicating a substantial survival benefit when used earlier.
Scenario analyses consistently demonstrated the survival advantage of administering cilta-cel in earlier treatment lines for len-refractory MM patients.
These findings support the strategic use of cilta-cel in earlier treatment lines to optimize survival outcomes in relapsed/refractory MM.

Clinical relevance: Important but Not Practice Changing

While the data indicates a promising benefit of using cilta-cel earlier in the treatment pathway, the reliance on simulation models and the need for further real-world validation mean that these findings are important but not yet practice changing. Additional studies and real-world data are needed to confirm these results and facilitate integration into clinical practice.

Link to Abstract PF765

Abstract Number: PF766

COMPREHENSIVE ANALYSIS OF SOLUBLE BCMA AS A TUMOR MARKER FOR MONITORING OF TUMOR BURDEN IN PATIENTS WITH MULTIPLE MYELOMA

Presenter: Masanori Toho
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Soluble BCMA (sBCMA) levels at diagnosis correlate with multiple myeloma (MM) stages, showing progressive increases across ISS and R-ISS stages, indicating its potential as a marker for tumor burden.
sBCMA levels are significantly higher in patients with the 1q+ cytogenetic abnormality, but not associated with other abnormalities like t(4;14) or Del(17p), suggesting specific prognostic value.
The optimal sBCMA cutoff for predicting 2-year progression-free survival (PFS) is 393.7 ng/mL, with high sBCMA levels linked to a median PFS of 30 months, compared to not reached for low levels, highlighting its prognostic utility.
sBCMA levels show weak correlations with total diffusion volume (tDV), total metabolic tumor volume (TMTV), and bone marrow plasma cell percentage (BMPC%), but significant changes across disease states, supporting its role in disease monitoring.
sBCMA is a promising, less invasive alternative to traditional methods like NGS and MFC for minimal residual disease (MRD) detection, with lower levels in deeper MRD states, enhancing its clinical applicability.

Clinical relevance: Important but Not Practice Changing

Overall, while the study provides valuable insights into the potential utility of sBCMA as a biomarker for MM, the evidence is not yet strong enough to change current clinical practice. Further research, including prospective trials, is necessary to confirm these findings and establish sBCMA as a reliable tool in clinical settings.

Link to Abstract PF766

Abstract Number: PF767

QUADRUPLET DARATUMUMAB IN COMBINATION WITH BORTEZOMIB, LENALIDOMIDE, AND DEXAMETHASONE AS FRONT-LINE REGIMEN IMPROVED CLINICAL OUTCOMES IN HIGH-RISK MYELOMA PATIENTS IN CHINA: A MULTI-CENTERED PROSPECTIVE REAL-WORLD STUDY.

Presenter: Junling Zhuang
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

DVRd regimen showed superior clinical outcomes compared to VRd in newly diagnosed multiple myeloma (NDMM) patients, with a higher complete response rate before ASCT (58.7% vs 45.6%, P<0.001).
The 1-year progression-free survival (PFS) and overall survival (OS) rates were significantly higher in the DVRd group compared to the VRd group (PFS: 92% vs 84.5%, P=0.029; OS: 100% vs 93%, P=0.054).
Subgroup analysis revealed that DVRd provided greater benefits for patients with high-risk cytogenetic abnormalities (HRCAs), particularly those with 17p- (1-year PFS: 90% vs 85%, P=0.027; 1-year OS: 100% vs 75%, P=0.007).
In non-ASCT patients, DVRd showed a trend towards better 1-year PFS and OS rates compared to VRd, though not statistically significant (PFS: 89% vs 80%, P=0.079; OS: 100% vs 92%, P=0.091).
Adverse events were manageable, with similar incidence rates in both groups, primarily infections and peripheral neuropathy, supporting DVRd as a viable front-line treatment option in China.

Clinical relevance: Important but Not Practice Changing

Overall, while the study provides important insights into the potential benefits of the DVRd regimen, particularly for high-risk patients, the current evidence is not sufficient to change clinical practice. Further research is needed to establish the regimen's role in the standard treatment landscape for newly diagnosed multiple myeloma.

Link to Abstract PF767

Abstract Number: PF770

REALITEC SUBGROUP ANALYSIS: A MULTI-COUNTRY OBSERVATIONAL RETROSPECTIVE STUDY OF TECLISTAMAB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA OUTSIDE OF CLINICAL TRIALS

Presenter: Dr. Rakesh Popat
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

The REALiTEC study, involving 113 patients across 8 countries, showed an overall response rate (ORR) of 60.2% for teclistamab in relapsed/refractory multiple myeloma, with 52.2% achieving very good partial response (≥VGPR).
Median duration of response (DoR) was 20.3 months, progression-free survival (PFS) was 9.7 months, and overall survival (OS) was 26.2 months, indicating durable efficacy outside clinical trials.
Patients previously exposed to BCMA-directed treatments had a 52.6% ORR, with similar PFS, OS, and DoR compared to the overall population, though prior ADC exposure negatively impacted PFS and OS.
Subgroups with historically poorer outcomes, such as penta-refractory patients and those with high-risk cytogenetics, showed no significant differences in effectiveness, supporting teclistamab's broad applicability.
Patients eligible for MajesTEC-1 had significantly better PFS, OS, and DoR, highlighting the importance of patient selection in optimizing outcomes with teclistamab.

Clinical relevance: Important but Not Practice Changing

Overall, while the study provides important insights into the use of teclistamab outside of clinical trials and supports its effectiveness in a broader patient population, it does not present evidence strong enough to alter current clinical practice. Further prospective studies or RCTs would be needed to substantiate any practice-changing claims.

Link to Abstract PF770

Abstract Number: PF771

EFFICACY AND SAFETY OF LESS FREQUENT DOSING WITH ELRANATAMAB (ELRA) IN PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM): A US SUBGROUP ANALYSIS FROM MAGNETISMM-3

Presenter: Dr. Noopur Raje
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

In the US subgroup of the MagnetisMM-3 study, elranatamab (ELRA) achieved an overall response rate (ORR) of 66.0%, with 42.6% of patients achieving complete response or better.
The median progression-free survival (mPFS) was 27.3 months, and the median overall survival (mOS) was not reached, with a 30-month survival probability of 55.8%.
Patients were heavily pretreated, with 93.6% being triple-class refractory and 46.8% penta-drug refractory, highlighting ELRA's efficacy in a challenging patient population.
Treatment-emergent adverse events occurred in all patients, with 78.7% experiencing grade 3/4 events; infections were common, necessitating prophylactic measures.
Cytokine release syndrome (CRS) was observed in 61.7% of patients, but only at grades 1 and 2, indicating manageable safety concerns.

Clinical relevance: Important but Not Practice Changing

Overall, while the study provides valuable insights into the potential of ELRA for RRMM, the evidence is not yet strong enough to change clinical practice. Further research, including larger phase 3 trials, is needed to confirm these findings and establish ELRA as a standard treatment option.

Link to Abstract PF771

Abstract Number: PF776

INDIRECT COMPARISON OF LINVOSELTAMAB VERSUS ELRANATAMAB FOR TRIPLE-CLASS EXPOSED RELAPSED/REFRACTORY MULTIPLE MYELOMA

Presenter: Prof. Dr. Sundar Jagannath
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Linvoseltamab demonstrated statistically significantly higher objective response rate (ORR) and complete response (≥CR) rate compared to elranatamab in triple-class exposed relapsed/refractory multiple myeloma (TCE RRMM) patients.
Linvoseltamab showed a numerically higher rate of very good partial response or better (≥VGPR), and longer duration of response (DOR), progression-free survival (PFS), and overall survival (OS) than elranatamab.
Findings were consistent across additional matching-adjusted indirect comparisons (MAICs), including analyses with all prespecified prognostic factors and subgroups with ECOG performance status 0/1.
Despite a shorter follow-up period for linvoseltamab, results suggest its potential as a highly effective treatment option for TCE RRMM.

Clinical relevance: Important but Not Practice-Changing

In summary, while the results provide valuable comparative insights and suggest linvoseltamab may be a highly effective option for TCE RRMM, the limitations of the indirect comparison and available data mean these findings are not yet practice-changing.

Link to Abstract PF776

Abstract Number: PF781

STEM CELL TRANSPLANTATION IN FIT ELDERLY MULTIPLE MYELOMA PATIENTS IS SAFE AND EFFECTIVE, A REAL-WORLD AGE GROUP COMPARISON

Presenter: Koen Klomberg
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

In a cohort of 394 multiple myeloma patients, those over 65 years showed comparable median overall survival (OS) of 101 months to those 65 or younger, who had a median OS of 116 months (p=0.56).
The median time to next treatment or death (TTNT-D) was similar between age groups, with 41 months for patients over 65 and 38 months for those 65 or younger (p=0.78).
At day 100 post-transplant, 85% of older patients achieved at least a very good partial response (VGPR), comparable to 89% in younger patients, indicating similar treatment efficacy.
Serious complications were infrequent, with a transplant-related mortality rate of 1% and secondary primary malignancies occurring in 10% of patients, showing a manageable safety profile.
Quality of life assessments revealed stable to increasing trends over the long term, with similar scores between age groups, supporting the feasibility of HDT/ASCT in fit elderly patients.

Clinical relevance: Important but Not Practice Changing

While the study provides important real-world evidence supporting the use of HDT/ASCT in fit elderly MM patients, it does not present new data strong enough to change clinical practice. It reinforces existing practices and may influence decision-making in borderline cases, but further prospective studies are needed to establish definitive guidelines for this population.

Link to Abstract PF781

Abstract Number: PF783

BELANTAMAB FOR THE TREATMENT OF MULTIPLE MYELOMA: RESULTS FROM PART 1 OF THE FIRST-IN-HUMAN PHASE 1/2 DREAMM-20 TRIAL

Presenter: Hang Quach
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

No dose-limiting toxicities (DLTs), treatment-related adverse events (TRAEs) leading to discontinuation, or belantamab-related grade ≥2 corneal events were observed; most common TRAEs were infusion-related reactions and hematologic events.
Overall response rate (ORR) was 28% (5/18 patients) across all dose cohorts, with durable responses (median exposure in responders: 8.3 months) and no disease progression among responders at data cutoff.
Belantamab demonstrated dose-proportional pharmacokinetics and on-target biological activity, evidenced by changes in circulating plasmablast levels.
Results support clinical activity and an acceptable safety profile for belantamab in heavily pretreated, triple-class–exposed relapsed/refractory multiple myeloma patients; further evaluation is ongoing in part 2 of DREAMM-20.

Clinical relevance: Interesting but Limited Impact

In summary, while the study provides early evidence of safety and some clinical activity for unconjugated belantamab in a difficult-to-treat population, the data are preliminary and insufficient to influence current clinical practice or challenge existing standards. The findings are hypothesis-generating and warrant further investigation in larger, controlled trials.

Link to Abstract PF783

Abstract Number: PF790

REAL-WORLD CHARACTERISTICS AND SAFETY AND EFFECTIVENESS OF TALQUETAMAB AMONG PATIENTS WITH RELAPSED OR REFRACTORY MULTIPLE MYELOMA (RRMM): AN ELECTRONIC MEDICAL RECORD AND CHART REVIEW STUDY

Presenter: Cesar Rodriguez
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

In a real-world study of 125 patients with relapsed or refractory multiple myeloma (RRMM) initiating talquetamab (TAL), the real-world overall response rate (rwORR) was 77% among 83 response-evaluable patients, consistent with the pivotal trial results.
The median duration of response (DoR) was not reached, with 55% of patients maintaining response at 12 months, and the median progression-free survival (PFS) was 6.2 months.
The median overall survival (OS) was not reached, with a 71% OS rate at 12 months, indicating promising long-term outcomes.
Common adverse events included cytokine release syndrome (CRS) in 57% of patients and dysgeusia in 81%, with most CRS events being mild and dysgeusia improving in 65% of cases within a median of 78 days.
These findings support TAL as an effective treatment option for RRMM, with real-world effectiveness aligning with clinical trial data.

Clinical relevance: Important but Not Practice Changing

While the study provides valuable real-world data supporting the use of talquetamab, it does not introduce new evidence strong enough to change current clinical practice. The findings are important for confirming the effectiveness and safety of TAL in a real-world setting but do not surpass the existing standard-of-care treatments or provide new insights that would alter treatment protocols.

Link to Abstract PF790

Abstract Number: PF792

PREDICTING CARDIAC AND RENAL RESPONSE IN LIGHT CHAIN (AL) AMYLOIDOSIS USING AN ENSEMBLE MACHINE LEARNING MODEL

Presenter: Louis Williams
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

XGBoost significantly outperformed logistic regression (LR) in predicting cardiac and renal responses in AL amyloidosis, with higher AUC and accuracy at all time points, notably at 6 months for cardiac response (AUC 0.83 vs. 0.61; accuracy 85.4% vs. 63.0%).
For renal response, XGBoost consistently showed superior predictive capability, achieving an AUC of 0.77 and accuracy of 81.9% at 6 months, compared to LR (AUC 0.68; accuracy 70.8%).
Key predictors for cardiac response at 6 months included 24-hour urine protein, serum M-protein, and age, with higher urine protein levels (>5g/24h) reducing response likelihood.
XGBoost demonstrated higher sensitivity (94% vs. 67%) and specificity (73% vs. 56%) for predicting cardiac response at 6 months compared to LR.
The study highlights XGBoost's ability to capture non-linear relationships and identify novel predictors, offering advancements in risk stratification and personalized treatment strategies for AL amyloidosis.

Clinical relevance: Important but Not Practice Changing

While the study presents valuable insights into the use of machine learning for predicting organ response in AL amyloidosis, the findings are not yet strong enough to change clinical practice. Further prospective validation and demonstration of clinical impact are needed before such models can be routinely implemented in patient care.

Link to Abstract PF792

Abstract Number: PF1225

RATES OF INFLUENZA AND PNEUMOCOCCAL VACCINATION AND CORRELATION WITH SURVIVAL IN MULTIPLE MYELOMA PATIENTS: A REAL-LIFE SURVEY

Presenter: Dr. Alessandra Romano
Session: Infections in hematology (incl. supportive care/therapy)

Abstract Summary:

Influenza vaccination (FV) was administered to over 70% of multiple myeloma (MM) patients, while less than 50% received pneumococcal vaccination (PV), often with suboptimal sequencing.
Vaccinated patients showed a lower incidence of infections, with 76% experiencing no infections compared to 57% of non-vaccinated patients; hospitalization rates were also lower among vaccinated individuals.
Anti-pneumococcal antibody responses were observed in 85% of patients, with a threefold increase in antibody concentration post-vaccination, although levels decreased over time.
Vaccination significantly reduced infection-related mortality, with FV and PV associated with lower death rates (FV: 5.8% vs. 12.5%, PV: 9.6% vs. 17.0%) and improved overall survival (FV: HR 0.71, PV: HR 0.56).
Despite preexisting hypogammaglobulinemia, MM patients responded to PV, indicating the need for a tailored vaccination schedule, particularly for relapsed/refractory MM patients.

Clinical relevance: Important but Not Practice Changing

While the study provides important evidence supporting the benefits of vaccination in MM patients, it primarily reinforces existing guidelines rather than introducing a new standard of care. The findings are valuable for encouraging adherence to vaccination recommendations but do not warrant an immediate change in clinical practice.

Link to Abstract PF1225

Abstract Number: PS1673

SELECTIVE DEPLETION OF B-CELL LINEAGE SUBSETS DURING TREATMENT WITH ANTI-BCMA VS ANTI-GPRC5D BISPECIFIC ANTIBODIES (BSABS) UNDERLIES DIFFERENT RISK OF INFECTIONS IN PATIENTS WITH MULTIPLE MYELOMA (MM)

Presenter: Dr. Tomas Jelinek
Session: Myeloma and other monoclonal gammopathies - Biology & translational research

Abstract Summary:

Anti-BCMA bispecific antibodies (bsAbs) are linked to a higher infection rate (82% vs. 53%; p=0.012) and more profound hypogammaglobulinemia compared to anti-GPRC5D bsAbs, necessitating more frequent IVIG replacement (74% vs. 32%; p=0.001).
During treatment, anti-BCMA bsAbs cause significant depletion of mature B cells and normal plasma cells (PCs), unlike anti-GPRC5D bsAbs, which show limited expression in normal PCs.
BCMA is expressed on mature B cells and unexpectedly on B cell precursors, with the highest expression in small pre-B2 cells, leading to their depletion and accumulation of pre-B1 cells during anti-BCMA treatment.
Interruption of anti-BCMA bsAbs therapy is necessary for the regeneration of the B cell compartment, as depletion persists throughout treatment.
These findings suggest that the distinct expression patterns of BCMA and GPRC5D contribute to different on-target off-tumor effects, informing the management of bsAbs-treated patients, including individualized IVIG prophylaxis.

Clinical relevance: Important but Not Practice Changing

Overall, while the study provides important insights into the differential risks associated with anti-BCMA and anti-GPRC5D bsAbs, it does not present evidence strong enough to change current clinical practice. Instead, it highlights the need for careful management of infection risks in patients treated with anti-BCMA bsAbs.

Link to Abstract PS1673

Abstract Number: PS1711

UPDATED RESULTS OF A PHASE I OPEN-LABEL SINGLE-ARM STUDY OF DUAL TARGETING BCMA AND CD19 FASTCAR-T (GC012F/AZD0120) AS FIRST-LINE THERAPY FOR TRANSPLANT-ELIGIBLE NEWLY DIAGNOSED HIGH-RISK MULTIPLE MYELOMA

Presenter: Juan Du
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

GC012F/AZD0120 CAR-T therapy achieved a 100% overall response rate (ORR) and a 95.5% stringent complete response (sCR) rate in transplant-eligible high-risk newly diagnosed multiple myeloma (NDMM) patients.
All patients achieved minimal residual disease (MRD) negativity, with sustained MRD negativity rates of 100%, 95%, and 87% at 1, 12, and 24 months, respectively.
At a median follow-up of 32.3 months, the median duration of response (DOR) and progression-free survival (PFS) have not been reached, with a PFS rate of 85.7% at 30 months.
Safety profile was favorable, with only 27% experiencing low-grade cytokine release syndrome (CRS) and no cases of grade ≥3 CRS or ICANS observed.
The study underscores the potential of GC012F/AZD0120 as a first-line therapy for high-risk NDMM, warranting further research with larger cohorts and longer follow-up.

Clinical relevance: Important but Not Practice Changing

Overall, while the study presents promising early-phase data with high response rates and a favorable safety profile, the lack of a control group and the small sample size limit its immediate impact on clinical practice. Further research, including larger randomized controlled trials, is necessary to validate these findings and potentially alter the standard of care for high-risk NDMM patients.

Link to Abstract PS1711

Abstract Number: PS1713

ELEVATED PROPORTIONS OF RESIDUAL BONE MARROW CLONAL PLASMA CELLS IN S-PHASE PRIOR TO AUTOLOGOUS STEM CELL TRANSPLANTATION IS ASSOCIATED WITH HIGH RISK OF EARLIER RELAPSE IN MULTIPLE MYELOMA PATIENTS

Presenter: Tamer Hellou
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Residual clonal plasma cells in S-phase prior to ASCT are associated with earlier relapse in multiple myeloma patients, with higher S% correlating with shorter time to progression (TTP).
Patients with S% ≥10% had a median TTP of 4 months and a median overall survival (OS) of 10 months, indicating a significantly poorer prognosis compared to those with lower S%.
Multivariate analysis showed that each 1% increase in S% was linked to a 16% increase in the hazard of progression, underscoring the prognostic value of S% as a continuous variable.
No significant difference in TTP was observed between patients with S% <2% and those with S% of 2-4.9%, suggesting a threshold effect at higher S% levels.
The study highlights the need for novel consolidation strategies for patients with highly proliferative clonal plasma cells to improve post-ASCT outcomes.

Clinical relevance: Important but Not Practice Changing

Overall, the study offers important insights into the prognostic significance of clonal plasma cell proliferation in multiple myeloma patients undergoing ASCT. However, it does not yet provide sufficient evidence to change clinical practice, as further research is needed to explore and validate alternative consolidation strategies for patients with high S%.

Link to Abstract PS1713

Abstract Number: PS1716

LINVOSELTAMAB + BORTEZOMIB IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: INITIAL RESULTS FROM THE LINKER-MM2 TRIAL

Presenter: Dr. Paula Rodríguez-Otero
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

LINVOSELTAMAB plus bortezomib achieved a high objective response rate (ORR) of 79% (11/14 evaluable patients) in relapsed/refractory multiple myeloma, including 86% with triple-class exposure and 41% with triple-class refractory disease.
Six-month duration of response (DOR) rate was 90% and six-month progression-free survival (PFS) rate was 79%, indicating encouraging early efficacy in a heavily pretreated, proteasome inhibitor–refractory population.
Safety profile was consistent with known effects of each agent; most common grade 3-4 treatment-emergent adverse events were neutropenia (45%), thrombocytopenia (36%), and infections (36%). Cytokine release syndrome occurred in 55% (all grade 1-2), and ICANS was limited to grade 1-2 events.
Risk of grade 3–5 infection was similar to LINVO monotherapy, and pharmacokinetics of LINVO were not affected by bortezomib co-administration.
Findings support further exploration of LINVO-based combinations in earlier lines of therapy.

Clinical relevance: Interesting but Limited Impact

In summary, while the combination of linvoseltamab and bortezomib demonstrates encouraging early efficacy and a manageable safety profile in a difficult-to-treat population, the data are preliminary and not robust enough to influence clinical practice. Larger, randomized studies with longer follow-up are needed to establish clinical benefit and comparative value.

Link to Abstract PS1716

Abstract Number: PS1717

NARLUMOSBART COMPARED WITH DENOSUMAB IN THE TREATMENT OF BONE DISEASE IN PATIENTS WITH MULTIPLE MYELOMA: A MULTICENTER, RANDOMIZED, CONTROLLED, NON-INFERIORITY STUDY

Presenter: Fei Li
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Narlumosbart demonstrated non-inferiority to denosumab in reducing urinary N-terminal telopeptide of type 1 collagen corrected for urine creatinine (uNTx/uCr) in patients with multiple myeloma, with 89.0% of patients achieving a >65% reduction compared to 85.0% in the denosumab group.
Both treatment groups showed substantial decreases in uNTx/uCr after the first dose, maintaining this trend through week 13, with similar median percentage changes in bone alkaline phosphatase and serum C-terminal telopeptide of type 1 collagen.
Only one patient in the narlumosbart group experienced an on-study skeletal-related event (SRE), with median time to first on-study SRE not estimable for either group.
Treatment-emergent adverse events (TEAEs) were reported in 63.5% of narlumosbart-treated patients and 74.4% of denosumab-treated patients, with grade 3/4 TEAEs occurring in 13.9% and 19.8% of patients, respectively.
No cases of osteonecrosis of the jaw were reported, and hypocalcemia was managed with calcium and/or vitamin D supplementation.

Clinical relevance: Important but Not Practice Changing

Overall, the study contributes valuable information about a new treatment option for bone disease in multiple myeloma, but the findings are not strong enough to change current clinical practice. Further research is needed to establish any potential advantages of narlumosbart over existing therapies.

Link to Abstract PS1717

Abstract Number: PS1719

IMPACT OF MASS SPECTROMETRY ON THE EVALUATION OF MAINTENANCE TREATMENT IN PATIENTS WITH MYELOMA ENROLLED IN THE GEM2014MAIN TRIAL: INSIGHTS INTO TREATMENT RESPONSE AND DISEASE PROGRESSION

Presenter: Noemi Puig
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Mass spectrometry (MS) effectively distinguished two patient groups with different progression-free survival (PFS) outcomes after 24 cycles of maintenance therapy, with MS-positive patients having a median PFS of 5.2 years, while PFS was not reached in MS-negative patients (p=0.0012; HR=0.331).
Patients who remained consistently MS-negative had excellent outcomes, with only 8.75% relapsing by year six, compared to a 22% relapse rate in the overall MS-negative cohort.
MS-negative patients who later converted to MS-positive experienced earlier relapses, with a median PFS of 3.4 years, similar to those who were always MS-positive, indicating the prognostic significance of MS status changes.
Among patients experiencing disease progression, 35% were constantly MS-positive, and 67% had converted from MS-negative to MS-positive, with a median time of 123 days from the first MS-positive result to clinical progression.
MS provides real-time insights into disease dynamics, suggesting its potential incorporation into myeloma management to personalize treatment strategies and optimize maintenance therapy duration.

Clinical relevance: Important but Not Practice Changing

While the study provides valuable insights into the use of MS for monitoring myeloma, further research and validation are needed before it can be considered practice changing. The findings contribute meaningfully to the field and highlight the potential for MS to enhance patient management, but they do not yet warrant a change in clinical practice.

Link to Abstract PS1719

Abstract Number: PS1720

DELETION 17P, AND IGH HIGH RISK TRANSLOCATIONS ALONG WITH CHROMOSOME 1 ABNORMALITIES ARE THE STRONGEST SURVIVAL PREDICTORS IN MULTIPLE MYELOMA: A REAL-WORLD VALIDATION BY THE GREEK MYELOMA STUDY GROUP

Presenter: Dr. Eirini Katodritou
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Deletion 17p and IgH high-risk translocations (IgH-HRT) combined with chromosome 1 abnormalities (1q21+ and/or del1p32) are the strongest predictors of overall survival (OS) in multiple myeloma, outperforming traditional staging systems like ISS, RISS, and R2ISS.
Patients with IgH-HRT plus 1q21+ and/or del1p32 and those with del17p had significantly shorter progression-free survival (PFS) and OS compared to low-risk patients, highlighting the critical impact of these genetic abnormalities.
In multivariate analysis, IgH-HRT plus 1q21+ and/or del1p32 and del17p were the most significant prognostic factors for OS, with hazard ratios of 2.75 and 2.76, respectively, indicating a strong negative impact on survival.
Single IgH-HRT or isolated chromosome 1 abnormalities did not significantly affect OS, suggesting that the combination of primary and secondary genetic abnormalities is crucial for prognosis in multiple myeloma.
Deletion 17p retained its prognostic significance across both transplant-eligible and ineligible groups, regardless of modern therapies, underscoring its pivotal role in predicting outcomes in multiple myeloma.

Clinical relevance: Important but Not Practice Changing

Overall, while the study provides valuable validation of prognostic factors in a real-world setting, it does not introduce new treatment paradigms or significantly alter existing clinical practices. Therefore, it is classified as important but not practice changing.

Link to Abstract PS1720

Abstract Number: PS1724

EFFICACY AND SAFETY OF FRONTLINE ALTERNATING BORTEZOMIB-BASED REGIMENS PLUS DARATUMUMAB IN PRIMARY PLASMA CELL LEUKEMIA: INTERIM RESULTS OF EUMELEIA PHASE 2 TRIAL BY THE GREEK MYELOMA STUDY GROUP.

Presenter: Dr. Eirini Katodritou
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

The interim analysis of the EUMELEIA Phase 2 trial shows a 100% overall response rate in primary plasma cell leukemia (pPCL) patients treated with alternating D-PAD/D-CVD regimens combined with daratumumab (DARA), with 21.1% achieving complete response and 73.7% achieving very good partial response.
Minimal residual disease (MRD) negativity was observed in bone marrow in 2 out of 5 patients assessed and in peripheral blood in all 7 patients examined, indicating deep responses.
Grade ≥3 adverse events were reported in 45% of patients, primarily cytopenias and infections, with one treatment-unrelated death due to respiratory infection.
The study supports the efficacy and safety of the D-PAD/D-CVD induction regimen in the first-line setting for pPCL, with further results from a larger cohort and longer follow-up needed to confirm these findings.
The trial highlights the potential of integrating DARA into existing regimens to enhance response depth and improve survival outcomes in pPCL.

Clinical relevance: Important but Not Practice Changing

While the interim results are promising and suggest a potential improvement in treatment outcomes for pPCL, the lack of a control group, small sample size, and early stage of the research mean that these findings are not yet strong enough to change clinical practice. Further data from the complete cohort and longer follow-up are needed to confirm these results and establish their place in the treatment landscape.

Link to Abstract PS1724

Abstract Number: PS1728

ABSOLUTE LYMPHOCYTE COUNT AS A KEY BIOMARKER FOR MONITORING SAFETY AFTER CILTACABTAGENE AUTOLEUCEL

Presenter: Yi Lin
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Elevated absolute lymphocyte count (ALC) at early time points post-infusion is strongly associated with the development of movement and neurocognitive treatment-emergent adverse events (MNT) and cranial nerve palsy (CNP) in patients receiving ciltacabtagene autoleucel (cilta-cel) for relapsed/refractory multiple myeloma (RRMM).
ALC and CAR-T cell counts peaked at a median of 14 days post-infusion, correlating significantly with each other, particularly on day 14, indicating a potential biomarker for monitoring adverse events.
Patients with MNT and CNP had significantly higher CAR-T cell counts and ALC on day 14 compared to controls, suggesting these metrics as predictive markers for adverse events.
Multivariate analyses identified ALC, CAR-T cell peak expansion, and CD4+ T-cell counts as factors associated with MNT and CNP, with ALC showing the strongest association.
ALC may serve as an early biomarker for identifying patients at risk for MNT and CNP, potentially guiding closer monitoring and preemptive interventions such as short-course dexamethasone.

Clinical relevance: Important but Not Practice Changing

While the study provides valuable insights into potential biomarkers for monitoring safety in CAR-T cell therapy, the findings are not yet robust enough to change clinical practice. Further research and validation are needed to confirm these biomarkers' utility and to develop standardized protocols for their use in clinical settings.

Link to Abstract PS1728

Abstract Number: PS1729

SIMULTANEOUS WHOLE-BODY MULTI-PARAMETRIC 2-[18F]FDG-PET/MRI IN SMOLDERING MULTIPLE MYELOMA ASSESSMENT : DIAGNOSTIC AND PROGNOSTIC IMPACT

Presenter: Bastien Jamet
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

WB-2-[18F]FDG-PET/MRI imaging significantly improved diagnostic accuracy in SMM, detecting diffuse bone marrow involvement (BMI) in 56% of patients, compared to 20% with PET alone and 53% with MRI alone.
Presence of MRI-detected diffuse BMI was the strongest adverse prognostic factor for progression-free survival (PFS), with a hazard ratio of 6.12, indicating a substantial risk of progression to symptomatic MM.
Dynamic contrast-enhanced (DCE) MRI features, such as peak enhancement intensity (PEI) and maximum intensity time ratio (MITR), were also identified as strong adverse prognostic factors for PFS.
Bone marrow plasma cell rate, particularly when exceeding 20%, was the only biological marker significantly associated with faster progression to symptomatic MM.
WB-2-[18F]FDG-PET/MRI imaging led to treatment initiation in over 15% of patients based solely on imaging findings, underscoring its potential as a critical tool in SMM management.

Clinical relevance: Important but Not Practice Changing

Overall, the study provides valuable insights into the use of advanced imaging for SMM, particularly in identifying high-risk patients. However, the findings are not yet robust enough to change clinical practice, as further validation and consideration of cost-effectiveness and accessibility are needed.

Link to Abstract PS1729

Abstract Number: PS1733

ENHANCED REAL-WORLD OUTCOMES IN MULTIPLE MYELOMA FOLLOWING IMPLEMENTATION OF ALCYONE, CASSIOPEIA, MAIA, AND PERSEUS PROTOCOLS IN SWEDISH NATIONAL GUIDELINES: DATA FROM THE SWEDISH MYELOMA REGISTRY (2008-2024)

Presenter: Dr. Cecilie Hveding Blimark
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Real-world data from the Swedish Myeloma Registry shows a significant increase in patients achieving ≥ Very Good Partial Response (VGPR) from 49% in 2008 to 86% in 2023 for those aged 18-70, and from 21% to 65% for those over 70.
Relative survival rates improved notably for patients diagnosed after 2017, with 9-year survival increasing from 40% to 69% in younger patients and 7-year survival from 21% to 36% in older patients.
Observed survival rates for patients diagnosed in 2017 and later were 93%, 85%, and 76% at 1, 3, and 5 years, respectively, for those aged ≤70, and 78%, 56%, and 38% for those over 70.
The implementation of modern treatment protocols, including VTD/VRD + daratumumab, has led to response rates comparable to clinical trials, with nearly 90% of younger patients achieving ≥ VGPR in 2023.
The study highlights the enhanced real-world outcomes in multiple myeloma following the integration of advanced therapies into Swedish national guidelines, particularly for non-transplant eligible and transplant-eligible patients.

Clinical relevance: Important but Not Practice Changing

While the study provides valuable real-world evidence supporting the effectiveness of current treatment regimens for NDMM, it does not introduce new therapies or mechanisms that would change clinical practice. The findings reinforce existing guidelines rather than alter them, making this study important but not practice changing.

Link to Abstract PS1733

Abstract Number: PS1734

DREAMM-7 STUDY OF BELANTAMAB MAFODOTIN + BORTEZOMIB + DEXAMETHASONE VS DARATUMUMAB + BORTEZOMIB + DEXAMETHASONE IN RELAPSED/REFRACTORY MULTIPLE MYELOMA: EFFICACY IN PATIENTS BY SUBSEQUENT THERAPY

Presenter: Prof. Dr. Vania Hungria
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

In the DREAMM-7 study, belantamab mafodotin combined with bortezomib and dexamethasone (BVd) showed significant improvements in progression-free survival (PFS) and overall survival (OS) compared to daratumumab with bortezomib and dexamethasone (DVd) in relapsed/refractory multiple myeloma, with a PFS hazard ratio (HR) of 0.41 and OS HR of 0.58.
Subsequent therapy analysis revealed that patients receiving anti-CD38 monoclonal antibodies, pomalidomide, or carfilzomib after BVd had a median time to progression or death of approximately 15 months, indicating effective post-BVd treatment outcomes.
In the intention-to-treat population, the 36-month OS rates were 74% for BVd and 60% for DVd, with median OS not reached, suggesting a sustained survival benefit with BVd.
Patients receiving subsequent anti-CD38 therapy post-BVd in the third-line or later setting had PFS comparable to those receiving DVd in the second-line or later, indicating similar benefits in later-line treatments.
The study highlights the efficacy of BVd in improving survival outcomes and the effectiveness of subsequent therapies in maintaining disease control in multiple myeloma.

Clinical relevance: Important but Not Practice Changing

Overall, while the study provides valuable insights into the potential benefits of BVd over DVd in relapsed/refractory multiple myeloma, the evidence is not yet strong enough to change current clinical practice. Further research and validation are needed to confirm these findings and to explore the long-term implications of using BVd as a standard treatment option.

Link to Abstract PS1734

Abstract Number: PS1736

TALQUETAMAB VS REAL-WORLD PHYSICIAN'S CHOICE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA AND PRIOR B-CELL MATURATION ANTIGEN THERAPY: UPDATED ANALYSES OF MONUMENTAL-1 VS LOCOMMOTION/MOMMENT

Presenter: Dr. María-Victoria Mateos
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Talquetamab demonstrated significantly higher overall response rates (ORR) compared to real-world physician's choice (RWPC) in patients with triple-class exposed relapsed/refractory multiple myeloma (TCE RRMM) and prior BCMA TCR exposure, with an observed ORR of 65.3% versus 11.1% and an adjusted relative risk (RR) of 6.39 (95% CI, 2.54-16.08; P<0.0001).
Progression-free survival (PFS) was notably improved with Talquetamab, showing a median PFS of 6.0 months compared to 2.5 months for RWPC, with an adjusted hazard ratio (HR) of 0.52 (95% CI, 0.28-0.95; P=0.0334), indicating a 48% reduced risk of progression or death.
Overall survival (OS) favored Talquetamab, with a median OS of 27.6 months versus 8.5 months for RWPC, and an adjusted HR of 0.32 (95% CI, 0.17-0.63; P=0.0008), reflecting a 68% reduced risk of death.
Sensitivity analyses confirmed the robustness of these findings, aligning with the base case analysis results.
These results reinforce Talquetamab as a superior treatment option for patients with TCE RRMM and prior BCMA TCR exposure, offering significant efficacy benefits over RWPC.

Clinical relevance: Important but Not Practice Changing

Overall, while the findings are significant and suggest Talquetamab as a potentially effective treatment for a specific patient population, the lack of randomized controlled trial data and the small sample size mean that these results are important but not yet sufficient to change clinical practice.

Link to Abstract PS1736

Abstract Number: PS1742

CYSTATIN C AS BIOMARKER FOR THE EVALUATION OF THE EVALUATION OF RENAL OUTCOME IN RENAL AL AMYLOIDOSIS

Presenter: Foteini Theodorakakou
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Cystatin C (CysC) levels at baseline were strongly correlated with creatinine (r=0.826, p<0.001) and eGFR-MDRD (r=-0.829, p<0.001), but not with proteinuria or serum albumin, indicating its potential as a reliable biomarker for renal function in AL amyloidosis.
Higher baseline CysC levels were significantly associated with progression to end-stage renal disease (ESRD) requiring dialysis, with a hazard ratio (HR) of 2.537 (p<0.001), and CysC≥1.9 mg/L was a strong predictor of ESRD risk at 2 years (HR 7.159, p<0.001).
In multivariate analysis, CysC was an independent prognostic factor for renal outcomes, alongside proteinuria, but not eGFR-MDRD, suggesting its utility in risk stratification.
Incorporating CysC≥1.9 mg/L into the Palladini staging system enhanced risk stratification, creating a 4-stage system that better identifies patients at high risk for ESRD.
CysC levels at 6 months and changes in CysC were strong predictors of renal progression, with an increase of ≥1 mg/L at 6 months associated with a significantly higher risk of ESRD (HR: 19.8, p<0.001).

Clinical relevance: Important but Not Practice Changing

Overall, while the findings are valuable and suggest that CysC could improve prognostic accuracy in renal AL amyloidosis, they do not yet provide sufficient evidence to change current clinical practice. Further validation in larger, diverse cohorts and integration into clinical guidelines are necessary before CysC can be considered a standard biomarker in this context.

Link to Abstract PS1742

Abstract Number: PS1743

POMALIDOMIDE, BORTEZOMIB AND DEXAMETHASONE (PVD) VERSUS BORTEZOMIB AND DEXAMETHASONE (VD) IN NDMM PATIENTS WITH RENAL INJURY(RI): A MULTICENTER, RANDOMIZED CONTROLLED, OPEN-LABEL TRIAL

Presenter: Prof. Dr. Jin Lu
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

The PVd regimen demonstrated superior efficacy in NDMM patients with renal injury, achieving a ≥VGPR rate of 70.91% compared to 21.74% in the Vd group.
Overall response rate (ORR) was significantly higher in the PVd group at 87.27% versus 43.48% in the Vd group, indicating a more effective treatment response.
Renal response was also better with PVd, with a major response rate (MRR) of 49.09% compared to 21.74% in the Vd group.
Adverse events were more frequent in the PVd group (82.76%) compared to the Vd group (66.67%), with 50% of PVd patients experiencing grade ≥3 severity.
This study supports the use of PVd over Vd in NDMM patients with renal impairment, with further data anticipated from extended follow-up.

Clinical relevance: Important but Not Practice Changing

Overall, while the study provides valuable insights into the treatment of NDMM with renal impairment, the evidence is not yet strong enough to change clinical practice. The findings highlight the potential of the PVd regimen but require further validation in larger, more comprehensive studies.

Link to Abstract PS1743

Abstract Number: PS1746

MULTICENTER PHASE 2 STUDY OF SUBCUTANEOUS ISATUXIMAB PLUS BORTEZOMIB, LENALIDOMIDE, AND DEXAMETHASONE (ISA SC-VRD) IN NEWLY DIAGNOSED TRANSPLANT-INELIGIBLE MULTIPLE MYELOMA (NDMM TI): RESULTS FROM ISASOCUT (IFM 2022-05)

Presenter: Arthur Bobin
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

The ISASOCUT study achieved its primary endpoint with an 87.8% ≥VGPR rate at 8 months in NDMM TI patients, aligning with previous studies like IMROZ and BENEFIT.
The ≥ complete response rate was 24%, and MRD negativity rates were 35.1% at 10⁻⁵ and 27% at 10⁻⁶, indicating strong efficacy of the Isa SC-VRd regimen.
At a median follow-up of 11.73 months, no relapses were reported, and survival data remain immature, with only 5% of patients discontinuing therapy.
Safety profile was favorable, with no new safety concerns; infusion-related reactions were mostly mild, and injection site reactions were predominantly grade 1.
High treatment adherence was observed, with a relative dose intensity of ≥90% for Isa SC, supporting Isa SC-VRd as a new standard of care for NDMM TI.

Clinical relevance: Important but Not Practice Changing

While the study provides valuable insights into the use of subcutaneous isatuximab in combination with VRd for NDMM TI patients, the findings do not yet warrant a change in clinical practice. The data are consistent with existing treatments, and the study's limitations, such as the small sample size and immature survival data, suggest that further research is needed to confirm these results and assess long-term outcomes.

Link to Abstract PS1746

Abstract Number: PS1774

CORRELATION ANALYSIS BETWEEN INTENSIVE FOLLOW-UP MANAGEMENT STRATEGIES AND PROGNOSIS IN PATIENTS WITH MULTIPLE MYELOMA

Presenter: Junling Zhuang
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Intensive follow-up management in newly diagnosed multiple myeloma (NDMM) patients significantly improved first-line progression-free survival (PFS-1), with a median of 30.4 months compared to 16.1 months in the non-intensive group (p<0.001).
The intensive follow-up group had a higher proportion of biochemical relapses (82.14%) compared to the non-intensive group (27.59%), indicating earlier detection and intervention (p<0.001).
Baseline characteristics were balanced after propensity score matching, ensuring comparability between the intensive and non-intensive follow-up groups.
Intensive follow-up management allowed for early identification of treatment-related toxicities and facilitated individualized treatment adjustments, contributing to improved patient compliance and outcomes.
The study suggests that the comprehensive follow-up protocol developed could be generalized to enhance management and prognosis in multiple myeloma patients.

Clinical relevance: Important but Not Practice Changing

Overall, while the study provides valuable insights into the benefits of intensive follow-up management in MM, the observational nature and limited matched sample size mean the findings are not yet strong enough to change clinical practice. However, they do suggest an area for further research and potential future practice improvements.

Link to Abstract PS1774

Abstract Number: PS1777

LONG-TERM FOLLOW-UP OF TANDEM AUTOLOGOUS VERSUS AUTOLOGOUS/ REDUCED-INTENSITY CONDITIONING ALLOGENEIC STEM CELL TRANSPLANTATION FROM RELATED OR UNRELATED DONORS IN FIRST-LINE THERAPY IN 149 PATIENTS WITH HIGH-RISK MYELOMA

Presenter: Song-Yau Wang
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

In high-risk multiple myeloma (HR MM) patients, median progression-free survival (PFS) and overall survival (OS) were similar between tandem autologous stem cell transplantation (ASCT) and reduced-intensity conditioning allogeneic stem cell transplantation (RICallo-SCT), with PFS of 36 vs. 33 months and OS of 78 vs. 80 months, respectively.
The ≥VGPR rate improved significantly post-transplant in both groups, from 61% to 83% in tandem ASCT and from 61.5% to 86.2% in RICallo-SCT.
Non-relapse mortality (NRM) was higher in the RICallo-SCT group, particularly within the first year, primarily due to acute graft-versus-host disease (GvHD) and treatment-related complications.
Matched related donor (MRD) RICallo-SCT showed a trend towards better long-term OS compared to tandem ASCT, with lower relapse mortality over ten years.
Matched unrelated donor (MUD) RICallo-SCT was associated with significantly higher treatment-related mortality and inferior OS compared to MRD, due to increased acute GvHD-triggered deaths.

Clinical relevance: Important but Not Practice Changing

While the study provides valuable insights into the potential benefits and risks of different transplantation strategies for high-risk MM patients, the evidence is not strong enough to warrant a change in clinical practice. The findings highlight the need for further prospective, randomized studies to better define the role of MRD RICallo-SCT in this patient population.

Link to Abstract PS1777

Abstract Number: PS1789

RENAL RESPONSE AND PROGNOSIS OF NEWLY DIAGNOSED MULTIPLE MYELOMA PATIENTS WITH RENAL IMPAIRMENT APPLYING VRD AND AUTOLOGOUS HAEMATOPOIETIC STEM CELL TRANSPLANTATION

Presenter: Chengcheng Fu
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

The VRD plus ASCT regimen demonstrated high efficacy in NDMM patients, achieving an overall response rate (ORR) of 93.7% and a ≥VGPR rate of 82.9%, regardless of renal impairment severity.
Renal remission was achieved in 70.8% of patients with baseline eGFR <50 ml/min, with complete remission (CR) in 31.5%, partial remission (PR) in 11.2%, and minimal response (MR) in 28.1%.
Patients with renal impairment, including those on dialysis, showed significant renal recovery, with 45.8% of dialysis-dependent patients being taken off dialysis during induction.
Despite more adverse events in patients with moderate-to-severe renal impairment during transplantation, ASCT improved prognosis, with better overall survival (OS) in patients achieving renal response (HR=0.3633, P=0.0491).
The presence of 1q21+ was identified as an independent factor negatively affecting renal function recovery (OR=3.58, P=0.03).

Clinical relevance: Important but Not Practice Changing

While the study provides valuable insights into the management of NDMM patients with renal impairment, the lack of randomization and the observational nature of the study mean that the findings, while important, do not yet warrant a change in clinical practice. Further RCTs are needed to confirm these results and potentially influence treatment guidelines.

Link to Abstract PS1789

Abstract Number: PS1792

THE EFFICACY AND SAFETY OF DARATUMUMAB-BASED REGIMENS IN THE INITIAL TREATMENT OF AMYLOID LIGHT-CHAIN AMYLOIDOSIS

Presenter: Kai Ding
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

Daratumumab-based regimens demonstrated a high hematologic overall response rate (ORR) of ≥95.4% and a complete response (CR) rate of 47.7% in AL amyloidosis, with a median time to response of 40 days and maximal response of 90 days.
Cardiac and renal response rates were 71.5% and 62%, respectively, with median times to response of 57 and 112 days, indicating significant efficacy in organ response.
Hematologic response and CR rates were significantly higher in the DVCD regimen compared to D+PI+DXM, with rates of 100% vs. 92.4% and 66.7% vs. 38.3%, respectively (p < 0.01).
The treatment was well-tolerated, with lymphopenia being the most common hematologic adverse reaction of ≥grade 3, and no non-hematologic adverse reactions of ≥grade 3 reported.
Daratumumab-based regimens showed promising efficacy as a first-line treatment for AL amyloidosis, surpassing conventional chemotherapy in response rates and speed, with no discontinuations due to adverse reactions.

Clinical relevance: Important but Not Practice Changing

While the study provides encouraging data on the efficacy and safety of daratumumab-based regimens for AL amyloidosis, the evidence is not yet strong enough to warrant a change in clinical practice. Further research, particularly prospective RCTs, is needed to confirm these findings and potentially alter the standard of care.

Link to Abstract PS1792

Abstract Number: PS1793

PHASE 3 DREAMM-10 STUDY DESIGN: BELANTAMAB MAFODOTIN PLUS LENALIDOMIDE AND DEXAMETHASONE VS DARATUMUMAB PLUS LENALIDOMIDE AND DEXAMETHASONE IN TRANSPLANT-INELIGIBLE NEWLY-DIAGNOSED MULTIPLE MYELOMA

Presenter: Prof. Dr. Meletios Dimopoulos
Session: Myeloma and other monoclonal gammopathies - Clinical

Abstract Summary:

DREAMM-10 is a randomized, phase 3, open-label study comparing belantamab mafodotin plus lenalidomide and dexamethasone (BRd) versus daratumumab plus lenalidomide and dexamethasone (DRd) in transplant-ineligible newly diagnosed multiple myeloma (TI-NDMM).
Primary endpoints are progression-free survival (PFS) and minimal residual disease (MRD) negativity rate; key secondary endpoints include overall survival and PFS2 (time to progression on subsequent therapy or death).
Approximately 520 patients will be randomized 1:1, stratified by age, International Staging System, and region; treatment continues until progression, death, unacceptable toxicity, withdrawal, or study end.
Belantamab mafodotin dosing: 1.9 mg/kg IV every 8 weeks for 24 weeks, then every 12 weeks; daratumumab administered per approved schedule; both arms receive standard lenalidomide and dexamethasone.
Study aims to address the unmet need for improved outcomes in TI-NDMM, leveraging prior evidence of belantamab mafodotin efficacy in combination regimens for relapsed/refractory MM.

Clinical relevance: Interesting but Limited Impact

In summary, while the DREAMM-10 trial is well-designed and addresses a clinically relevant question, this abstract provides no efficacy or safety data. Its impact is limited to informing the community of an ongoing trial and its methodology, without immediate implications for clinical practice or policy.

Link to Abstract PS1793