Here are the top journal articles from the week of June 24, 2021 as selected by the MYELOMA360 staff.
First-line Daratumumab in Addition to Chemotherapy for Newly Diagnosed Multiple Myeloma Patients Who are Transplant Ineligible: A Cost-Effectiveness Analysis.
Purpose: Daratumumab is a standard-of-care treatment for newly diagnosed multiple myeloma (NDMM). According to the ALCYONE trial, the addition of daratumumab to bortezomib, melphalan, and prednisone (D-VMP) provides significantly longer overall survival and progression-free survival than bortezomib, melphalan, and prednisone (VMP) in patients with NDMM. However, considering the high price of daratumumab, it is necessary to conduct further research on its efficacy and cost. This study evaluated the cost-effectiveness, from the US payer perspective, of D-VMP vs VMP in the first-line setting for patients with NDMM who are not eligible for autologous stem cell transplantation.
Methods: A Markov model was developed to estimate the lifetime cost and effectiveness of VMP with or without daratumumab as the first-line therapy for patients with NDMM. Univariable sensitivity analysis and probabilistic sensitivity analysis were performed to address the model robustness and uncertainty. Expected value of perfect information analysis was conducted to explore the uncertainty of decision-making and future costs.
Findings: D-VMP provides an additional 2.417 quality-adjusted life years (QALYs), at a cost of $30,893 per QALY. Sensitivity analysis revealed that the transition probability of progression-free survival in D-VMP strategy, the price of daratumumab, and body weight of the patient influenced the model results most strongly. Probabilistic sensitivity analysis showed that D-VMP versus VMP has a 90.8% probability of being cost-effective at the $150,000/QALY willingness-to-pay (WTP) threshold. The population expected value of perfect information was $2150 million at a WTP threshold of $50,000/QALY and $1481 million at $100,000/QALY.
Implications: In this study, D-VMP was estimated to be cost-effective compared with VMP for patients with NDMM at a WTP threshold of $150,000/QALY. (Clin Ther. 2021;43:XXX-XXX) © 2021 Elsevier HS Journals, Inc.
Keywords: Markov model; cost-effectiveness; daratumumab; multiple myeloma.
Prognostic Value of Galectin-9 Relates to Programmed Death-Ligand 1 in Patients With Multiple Myeloma
Galectin-9 (Gal-9) expression can be negatively or positively associated with cancer patient prognosis, depending on the cancer type. However, the nature of this relationship remains unclear in multiple myeloma. Therefore, we evaluated the prognostic value of Gal-9 and its relationship with the expression of PD-L1 molecule, the most widely studied immune checkpoint inhibitor, in patients with newly diagnosed multiple myeloma. Gal-9 and PD-L1 levels in bone marrow aspirate samples were evaluated using immunofluorescence assays. Gal-9 positivity was defined as having ≥1% Gal-9-expressing plasma cells. PD-L1 expression was categorized as low or high based on its median value. The median OS of patients with positive and negative Gal-9 expression was 42 months and not reached, respectively. However, no significant difference was observed in OS between the two groups (P = 0.10). Patients with high PD-L1 expression had OS times of 14 and 43 months in the positive and negative Gal-9 expression groups, respectively. In the high PD-L1 expression group, patients expressing Gal-9 had significantly worse OS than those negative for it (P = 0.019). Multivariable Cox analysis confirmed that Gal-9 expression could independently predict shortened OS (hazard ratio, 1.090; 95% confidence interval, 1.015-1.171; P = 0.018) in patients with high PD-L1 expression. However, in the low PD-L1 expression group, patients with high Gal-9 expression exhibited a trend toward better OS (P = 0.816). Our results indicate that the prognostic value of Gal-9 may be related to PD-L1 expression in patients with newly diagnosed multiple myeloma.
Keywords: galectin-9 (Gal-9); multiple myeloma; plasma cells; prognosis; programmed death-ligand 1 (PD-L1).
HLA-E Binding Peptide as a Potential Therapeutic Candidate for High-Risk Multiple Myeloma
Human leukocyte antigen-E (HLA-E) has been putatively associated with the pathogenesis of multiple myeloma (MM). Our study first showed that HLA-E was differentially expressed on MM and normal plasma cells (39.27 ± 27.01 and 11.28 ± 0.79, respectively). Based on the median value of HLA-E expression, we further stratified MM patients into high and low-expression groups, and then found high expression of HLA-E was correlated with advanced ISS stage (p = 0.025) and high-risk cytogenetics risk stratification (p = 0.000) by the Pearson Chi-square test, suggesting that HLA-E could be considered as a biomarker for high-risk MM. Furthermore, peptide 3 (P3) from our previous study was confirmed to possess a high affinity to HLA-E positive MM cells. Taken together, HLA-E could be considered as a new marker and candidate treatment target for MM, while peptide P3 may act as a potential treatment choice for targeting MM cells.
Different Patient Subgroup Different Maintenance, Proteasome Inhibitors or Immunomodulators Maintenance for Newly Diagnosed Multiple Myeloma: A 7-Year Single-Center Date in China
We analyzed different patient subgroups to determine optimal maintenance therapy in newly diagnosed multiple myeloma (NDMM) patients.
A total of 226 NDMM patients in our center were included in the study. The characteristics, survival, and adverse reactions were compared among patients who received maintenance therapy or not, and patients who received proteasome inhibitors (PIs) or immunomodulators (IMiDs) maintenance. The survival of different maintenance durations of bortezomib-based regimens was also analyzed.
The maintenance therapy not only upgraded more patient responses (34.3 vs 13.3%, P = 0.006), but also significantly prolonged their progression-free survival (PFS) (median PFS: 41.1 vs 10.5 months, P < 0.001) and overall survival (OS) (median OS: not reached vs 38.6 months, P < 0.001). Compared with IMiDs, the PFS (median PFS: 43.7 vs 38.5 months, P = 0.034) and OS (median OS: not reached vs 78.5 months, P = 0.041) were both enhanced by PIs maintenance. Patients younger than 65 years who received PIs had a significantly prolonged OS (P = 0.032). Patients achieving only a partial response (PR) after induction and consolidation therapy had significantly longer PFS and OS after PIs maintenance compared to IMiDs (P = 0.007, 0.002). High-risk patients (ISS 2–3, DS 2–3, and RISS 2–3) given PIs maintenance benefit from a prolonged PFS (P = 0.002, 0.02, 0.06) and OS (P = 0.059, 0.047, 0.044, respectively) compared with IMiDs therapy. OS was significantly prolonged in patients who received ≥ 12 months of bortezomib-based maintenance therapy compared to those who were treated for < 12 months (P < 0.001), but no difference was observed in OS between patients who received 12 to 24 or ≥ 24 months of bortezomib-based maintenance therapy (P = 0.292).
PIs maintenance was superior to IMiDs in overall PFS and OS. The beneficial effect was most evident in patients achieving PR after induction and consolidation therapy, and in high-risk patients. Moreover, younger patients also benefited from PIs maintenance with an increased OS. A bortezomib-based maintenance therapy duration of 12 to 24 months after induction and consolidation therapy produced satisfactory OS.
A personalized mass spectrometry-based assay to monitor M-protein in multiple myeloma patients (EasyM).
Purpose: M-protein is a well-established biomarker used for multiple myeloma (MM) monitoring. Current improvements in MM treatment created the need to monitor minimal residual disease (MRD) with high sensitivity. Measuring residual levels of M-protein in serum by mass spectrometry (MS) was established as a sensitive assay for disease monitoring. In this study we evaluated the performance of EasyM – a non-invasive, sensitive, MS-based assay for M-protein monitoring.
Experimental Design: Twenty-six patients enrolled in MCRN-001 clinical trial of 2 high dose alkylating agents as conditioning followed by lenalidomide maintenance were selected for the study. All selected patients achieved CR during treatment, while 5 experienced progressive disease on study. The M-protein of each patient was first sequenced from the diagnostic serum using our de novo protein sequencing platform. The patient-specific M-protein peptides were then measured by targeted MS assay to monitor the response to treatment.
Results: The M-protein doubling over 6 months measured by EasyM could predict the relapse in four out of five relapsed patients 2-11 months earlier than conventional testing. In 21 disease-free patients, the M-protein was still detectable by EasyM despite normal FLC and MRD negativity. Importantly, out of 72 MRD negative samples with CR status, 62 were positive by EasyM. The best sensitivity achieved by EasyM, detecting 0.58 mg/L of M-protein, was 1000- and 200-fold higher compared to SPEP and IFE, respectively.
Conclusions: EasyM was demonstrated to be a non-invasive, sensitive assay with superior performance compared to other assays, making it ideal for MM monitoring and relapse prediction.
Cyclophosphamide plus etoposide is a safe and effective mobilization regimen in patients with multiple myeloma
High-dose chemotherapy followed by autologous stem cell transplantation is a major component in the treatment of patients with multiple myeloma. As a prerequisite, the successful collection of a sufficient number of viable peripheral blood hematopoietic CD34+ cells is critical. A common standard protocol for mobilization is currently not defined and critically discussed especially in German-speaking Europe. In times of the Covid-19 pandemic, safe and effective strategies have to be chosen to minimize hospitalization times and severe courses. In this single-center retrospective analysis, safety and efficacy of cyclophosphamide plus etoposide (CE) and growth-factor support (n = 33) was compared to cyclophosphamide mono treatment and growth-factor support (n = 49) in 82 patients with multiple myeloma at first diagnosis. CE was superior to cyclophosphamide mono with a significantly higher number of collected CD34+ cells (15.46 × 106 CD34+ cells/kg vs. 9.92 × 106 CD34+ cells/kg), significantly faster engraftment of granulocytes after stem cell transplantation (day 10.5 vs. day 11.6), shorter duration of the inpatient stay (17.47 days vs. 19.16 days) and significantly less transfusions (8.82 % vs. 30.61 % patients receiving transfusions). The safety profile was comparable in both groups and in line with published data. We conclude that CE is a safe and highly effective mobilization protocol in patients with multiple myeloma at first diagnosis and appears to be superior to the commonly used cyclophosphamide mono regimen.
Keywords: Autologous stem cell transplantation; Hematopoetic stem cell transplantation; Mobilization chemotherapy; Multiple myeloma.
Novel immunotherapies in multiple myeloma – chances and challenges
In this review article, we summarize the latest data on antibody-drug conjugates, bispecific T-cell-engaging antibodies, and chimeric antigen receptor T cells in the treatment of multiple myeloma. We discuss the pivotal questions to be addressed as these new immunotherapies become standard agents in the management of multiple myeloma. We also focus on the selection of patients for these therapies and speculate as to how best to individualize treatment approaches. We see these novel immunotherapies as representing a paradigm shift. However, despite the promising preliminary data, many open issues remain to be evaluated in future trials.
Long term follow up of newly diagnosed multiple myeloma patients treated with pembrolizumab consolidation post-autologous stem cell transplantation
Health-related quality of life outcomes from the CANDOR study in patients with relapsed or refractory multiple myeloma
CANDOR (NCT03158688) compared carfilzomib, dexamethasone, and daratumumab (KdD) to carfilzomib and dexamethasone (Kd) in patients with relapsed/refractory multiple myeloma (RRMM). A secondary objective of CANDOR was to evaluate health-related quality of life (HRQoL) scores using the Global Health Status (GHS)/Quality of Life (QoL) domain of the EORTC QLQ-C30. Scores were compared between KdD and Kd using a restricted maximum likelihood-based mixed effects model for repeated measures. GHS/QoL completion rates were >81% for both arms. Higher GHS/QoL scores were observed with KdD versus Kd from Cycle 7–26. The overall least squares mean estimate (95% CI) of the difference between treatment arms was 0.06 (–2.39 to 2.50; p = 0.96). In an exploratory analysis, 55.5% in the KdD arm and 43.0% in the Kd arm improved ≥10 points in GHS/QoL score from baseline. HRQoL was maintained with KdD, consistent with superior clinical benefit observed with KdD versus Kd in patients with RRMM.