Myeloma News
Cytokine-responsive T- and NK-cells portray SARS-CoV-2 vaccine-responders and infection in multiple myeloma patients
Gene interaction network analysis in multiple myeloma detects complex immune dysregulation associated with shorter survival
Belantamab Mafodotin Met Primary Endpoint for Those with Relapsed, Refractory Multiple Myeloma
Source: Pharmacy Times articles
Belantamab mafodotin (Blenrep; GlaxoSmithKline) demonstrated that, when combined with bortezomib and dexamethasone (BorDex), the time to disease progression or death was extended.
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A population-based study on incidence trends of myeloma in the United States over 2000–2020
Myeloma evades T cell-engaging therapies
CAR-T Therapy Responses, Toxicities Differ by Race Among Patients With Multiple Myeloma
Source: Myeloma – Hematology Advisor
A multicenter study found that response rates to the chimeric antigen receptor (CAR) T-cell therapy, idecabtagene vicleucel (ide-cel), varied by race/ethnicity, although progression-free survival (PFS) and overall survival (OS) were similar for patients with multiple myeloma (MM). In addition, the incidence of some toxicities, such as cytokine release syndrome (CRS), also varied by race/ethnicity. The results of the study were published in the journal Blood Advances.1
“In this study, we see that Black and White patients with MM both respond well to ide-cel,” author Laura Peres, PhD, said in a press release.2 “We hope that these findings encourage the use of ide-cel in all patients with MM.”
In the study, data from 207 patients with relapsed/refractory MM treated with ide-cel at 11 different institutions were analyzed to determine if race or ethnicity affected outcomes.1
The overall population included 10.6% of patients who were Hispanic, 17.4% who were non-Hispanic Black, and 72.0% who were non-Hispanic White. The median age at CAR-T therapy was 65 years for Black and White patients and 57 for Hispanic patients.
Extramedullary disease was present among 48% of patients and 56% had high-risk cytogenetics. Baseline characteristics were similar between the groups, except median levels of C-reactive protein was significantly higher among Black patients compared with White or Hispanic patients (P =.02) and preinfusion albumin levels were lower (P =.04).
The Hispanic cohort demonstrated lower overall response rates to ide-cel at 59% compared with 86% among the Black and 86% among the White cohorts (P =.01). However, a multivariate analysis found no association between race/ethnicity and achievement of a complete response or better. There was no significant difference between races/ethnicities and PFS or OS.
Any-grade CRS occurred among 97% of patients who were Black compared with 77% among patient who were Hispanic and 85% among patients who were White (P =.04). However, the rates of grade 3 or higher CRS were similar between the groups. In contrast, anakinra use occurred more frequently among patients who were Hispanic with a rate of 14% compared with 0% among Black patients and 5% among Whites (P =.06).
There was no significant difference in the rates of any grade or severe immune effector-cell associated neurotoxicity syndrome, hematologic toxicities, infection, or use of tocilizumab or steroids.
The length of hospital stay was longest among Black patients at a median of 13.5 days compared with 9.0 days among White patients and 8.0 days among Hispanic patients (P =.006). There was no difference in intensive care unit admission rates.
“Despite differences in safety and response to ide-cel, our findings encourage the use of ide-cel in all relapsed/refractory MM patients,” the study authors concluded.
Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of disclosures.
References
1. Peres LC, Oswald LB, Dillard CM, et al. Racial and ethnic differences in clinical outcomes among multiple myeloma patients treated with CAR T-cell therapy. Blood Adv. Published online October 16, 2023. doi: 10.1182/bloodadvances.2023010894
Minimizing Terms in Multiple Myeloma Clinical Trials May Inaccurately Reflect Tolerability, Rates of AEs
Source: Pharmacy Times articles
The study authors suggest that future research should instead emphasize event rates and patient-reported outcomes to better evaluate the tolerability and frequency of AEs.
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Anti-TACI single and dual-targeting CAR T cells overcome BCMA antigen loss in multiple myeloma
MRD-Negative MM Patients May Be Able to Stop Maintenance After 2 Years
Source: Myeloma – Hematology Advisor
Patients with multiple myeloma (MM) who achieve minimal residual disease (MRD) negativity can safely discontinue maintenance therapy after 2 years, according to research published in Blood.
Researchers found a low risk of disease recurrence at 4 years among patients who discontinued maintenance after receiving it for 2 years and achieving MRD negativity.
This study (ClinicalTrials.gov Identifier: NCT02406144) enrolled 332 patients with newly diagnosed MM who received induction with bortezomib, lenalidomide, and dexamethasone. This was followed by autologous stem cell transplant and consolidation with bortezomib, lenalidomide, and dexamethasone.
Patients were then randomly assigned to receive maintenance with either lenalidomide and dexamethasone (n=161) or ixazomib plus lenalidomide and dexamethasone (n=171). Patients could discontinue maintenance if they had an MRD-negative test result after 24 cycles. Patients who were MRD positive remained on maintenance for 36 more cycles.
At a median follow-up of 69 months, the median progression-free survival (PFS) was not reached in either treatment arm (hazard ratio [HR], 1.136; 95% CI, 0.809-1.603; P =.460). The 6-year PFS rate was 61.3% in the lenalidomide-dexamethasone arm and 55.6% in the ixazomib-lenalidomide-dexamethasone arm.
After 2 years of maintenance, 163 MRD-negative patients stopped treatment, and 63 MRD-positive patients continued on maintenance with lenalidomide and dexamethasone for 3 more years.
Despite the difference in discontinuation, the 4-year PFS rate was significantly higher in the MRD-negative patients than in the MRD-positive patients — 82.8% and 50.4%, respectively (HR, 0.253; 95% CI, 0.149-0.431; P <.0001).
The incidence of grade 3-4 thrombocytopenia was significantly higher in patients who received ixazomib than in those who did not — 16.3% and 7.4%, respectively (P =.011). Grade 3-4 gastrointestinal toxicities were also more common with ixazomib — 15.7% and 2.4%, respectively (P <.0001)
However, there were no significant between-arm differences in grade 3-4 neutropenia, infections, skin toxicities, fatigue, or deep vein thrombosis.
Based on these results, the researchers concluded that lenalidomide and dexamethasone is a “highly effective maintenance regimen” for this patient population.
“Maintenance discontinuation in patients who tested negative for MRD at 2 years resulted in a low progression rate, even in patients with initial high-risk features; however, the impact of treatment discontinuation in patients with undetectable MRD at 2 years should be formally confirmed by prospective randomized studies,” the researchers wrote.
Disclosures: This research was partly supported by Bristol Myers Squibb-Celgene and Takeda. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Reference
Rosiñol L, Oriol A, Ríos R, et al. Lenalidomide and dexamethasone maintenance with or without ixazomib, tailored by residual disease status in myeloma. Blood. Published online November 2, 2023. doi:10.1182/blood.2022019531
Interactions Between Tumor Genes, Microenvironment Impact Treatment Response in Multiple Myeloma
Source: Pharmacy Times articles
The study findings provide the first in-depth look at the relationship between chromosomal changes in tumor cells and immune components of the tumor microenvironment.
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Recent Publications
Advances in the pathogenesis of multiple myeloma bone disease
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2023 Sept 28;48(9):1403-1410. doi: 10.11817/j.issn.1672-7347.2023.220534. ABSTRACT Multiple myeloma (MM) is a clonal proliferative malignant tumor of plasma cells in bone marrow. With the aging of population in China, the incidence of MM is on the rise....
Association Between Circulating 25-Hydroxy Vitamin D Receptor and Molecular Response in Multiple Myeloma
Pak J Biol Sci. 2023 Aug;26(9):472-481. doi: 10.3923/pjbs.2023.472.481. ABSTRACT <b>Background and Objective:</b> Vitamin D Receptor (VDR) regulate several body processes related to metabolism, immunological function and oncogenesis. Low vitamin D levels are recognized...
Clinician preferences on treatment of smoldering myeloma: a cross-sectional survey
EClinicalMedicine. 2023 Oct 24;65:102272. doi: 10.1016/j.eclinm.2023.102272. eCollection 2023 Nov. ABSTRACT BACKGROUND: Smoldering myeloma (SMM) is an asymptomatic precursor condition to multiple myeloma (MM) with a variable risk of progression. The management of high-risk SMM (HR-SMM) remains...
Efficacy of different regimens and prognostic factors in patients with first relapsed multiple myeloma treated after front-line bortezomib, cyclophosphamide, and dexamethasone
Zhonghua Nei Ke Za Zhi. 2023 Dec 1;62(12):1436-1443. doi: 10.3760/cma.j.cn112138-20230619-00318. ABSTRACT Objective: To analyze the efficacy of second-line regimens and prognostic factors in patients with first-relapsed multiple myeloma (MM) treated with bortezomib, cyclophosphamide, and...
Impact of autologous stem cell transplantation (ASCT) on progression free survival (PFS) in newly diagnosed multiple myeloma patients (NDMM) with high risk cytogenetic abnormalities
Bratisl Lek Listy. 2024;125(1):9-11. doi: 10.4149/BLL_2024_002. ABSTRACT OBJECTIVES: ASCT has been considered the standard of care for younger patients with NDMM, however, not all the studies published so far have uniformly demonstrated the complete superiority of ASCT over chemotherapy at...
Clarithromycin overcomes stromal cell-mediated drug resistance against proteasome inhibitors in myeloma cells via autophagy flux blockage leading to high NOXA expression
PLoS One. 2023 Dec 1;18(12):e0295273. doi: 10.1371/journal.pone.0295273. eCollection 2023. ABSTRACT We previously reported that macrolide antibiotics, such as clarithromycin (CAM), blocked autophagy flux, and simultaneous proteasome and autophagy inhibition by bortezomib (BTZ) plus CAM resulted in...
Plasma levels of BCMA-positive extracellular vesicles correlate to response and side effects in myeloma patients treated with belantamab-mafodotin
Oncotarget. 2023 Dec 1;14:949-956. doi: 10.18632/oncotarget.28538. ABSTRACT In myeloma patients, high levels of soluble BCMA (sBCMA) can limit the efficacy of BCMA-directed therapies. Belantamab-mafodotin is a BCMA antibody-drug conjugate and shows good overall response rates in heavily pretreated...
Apparent diffusion coefficient measurements of bone marrow infiltration patterns in multiple myeloma for the assessment of tumor burden – a feasibility study
Radiol Oncol. 2023 Nov 30;57(4):455-464. doi: 10.2478/raon-2023-0048. eCollection 2023 Dec 1. ABSTRACT BACKGROUND: The purpose of our study was to explore and compare the tumor burden of different bone marrow infiltration patterns and evaluate the feasibility of apparent diffusion coefficient...
Expert Recommendations & Patient Perspectives for Treating Relapsed/Refractory Multiple Myeloma
In this webcast, expert faculty discuss best practices in treating patients with relapsed/refractory multiple myeloma and discuss the patient's perspective on treatment options. Learners will also get a look ahead at emerging therapeutic strategies and clinical trials...
Overview of Key Early-phase CAR T-cell Therapy Studies in Relapsed or Refractory Multiple Myeloma
In this article, we look at some of the early-phase clinical trials, where chimeric antigen receptor (CAR) T-cell therapy has been targeted to the B-cell maturation antigen (BCMA) in patients with relapsed or refractory MM (RRMM). The anti-BCMA CAR T-cell...
What Are Chimeric Antigen Receptor (CAR) T-cells and What is Their Potential Target Site in Multiple Myeloma?
CAR T-cell structure CARs are typically composed of four regions: (1) an extracellular antigen-binding domain; (2) a hinge or spacer peptide; (3) a transmembrane domain that anchors the CAR to the cell membrane; and (4) one or more intracellular signalling domains...