Bcma

B-cell maturation antigen (BCMA)-targeting immunotherapies (e.g., chimeric antigen receptor T cells (CAR-T) and bispecific antibodies (BsAbs)) have achieved remarkable clinical responses in patients with relapsed and/or refractory multiple myeloma (RRMM). Their use is accompanied by exaggerated immune responses related to T-cell activation and cytokine elevations leading to cytokine release syndrome (CRS) in some patients, which can be potentially life-threatening. However, systematic evaluation of the risk of CRS with BCMA-targeting BsAb and CAR-T therapies, and comparisons across different routes of BsAb administration (intravenous (i...

BACKGROUND: The outcome of patients with relapsed and refractory multiple myeloma (RRMM) previously treated with the three main classes of myeloma therapy [immunomodulatory drugs, proteasome inhibitors, and anti-CD38 antibodies] remains poor. Recently, based on the phase II pivotal KarMMa trial [showing prolonged overall survival (OS) and progression-free survival (PFS) among heavily treated patients], idecabtagene vicleucel (ide-cel), a B-cell maturation antigen (BCMA)- directed chimeric antigen receptor (CAR) T cell therapy has been approved in US for the treatment of RRMM...

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The objective of our study was to report real-world data on the safety and efficacy of standard-of-care teclistamab in patients with relapsed/refractory multiple myeloma (MM). This is a multi-institutional retrospective cohort study and included all consecutive patients that received at least one dose of teclistamab up until August 2023. One hundred and ten patients were included, of whom, 86% had triple-class refractory disease, 76% penta-refractory disease, and 35% had prior exposure to B-cell maturation antigen (BCMA)-targeting therapies...

Relapsed and refractory multiple myeloma (RRMM) and B-cell leukemia/lymphoma with extramedullary disease (EMD) have poor prognosis and high mortality, lack of effective therapeutic approaches. We reported for the first time that 6 patients with malignant hematological diseases with EMD received chimeric antigen receptor (CAR)-T treatment combined with pomalidomide, and CAR-T cells were treated with pomalidomide in vitro to determine its killing activity and cytokine secretion. Three patients with RRMM were given B cell maturation antigen (BCMA)-CAR-T therapy...

OBJECTIVES: Bispecific antibodies (BsAbs) are an effective treatment used in relapsed/refractory multiple myeloma. Despite a well-tolerated safety profile, infectious events appeared to be frequent in clinical trials. Real-world data on epidemiology, characteristics, risk factors and outcomes of infections in patients treated with BsAb are still needed. METHODS: A retrospective, multicenter study in BsAb-treated MM patients was conducted in 14 French centers from December 2020 to February 2023...

For patients with relapsed/refractory multiple myeloma (RRMM) with relapse following B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell therapies (CAR-T), optimal salvage treatment strategies remain unclear. BCMA-directed CAR-T and bispecific antibodies (BsAb) are now commercially available, and the outcomes for retreatment with BCMA-directed approaches are not well-studied. We performed a retrospective analysis of 68 patients with relapsed disease after BCMA-directed CAR-T to evaluate outcomes and responses to salvage therapies...

No abstract text is available yet for this article.

T cell engaging antibodies (TCEs) are showing promising efficacy in relapsed/refractory multiple myeloma (MM), even in patients that relapsed after BCMA targeted therapy. MM patients may have compromised T cell health unaccounted for by preclinical models. Here, we use Myeloma Drug Sensitivity Testing (My-DST) for ex vivo measurement of anti-MM cytotoxicity for the trispecific CD38/CD28xCD3 TCE SAR442257 through activation of the patients' own endogenous T cells to inform clinical development of the compound in MM...

The physical and emotional burden of relapsed or refractory multiple myeloma (RRMM) has been strongly correlated with declining health-related quality of life (QOL) in the patients it affects. This analysis evaluated patient-reported outcomes (PROs) from B-cell maturation antigen (BCMA)-naive (n = 123) and -exposed (n = 64) patients with RRMM enrolled in the MagnetisMM-3 study (NCT04649359) and treated with the humanized, bispecific BCMA-CD3 antibody elranatamab. Patients received two step-up doses of elranatamab (12 mg on day 1, 32 mg on day 4) before starting the full dose of 76 mg on day 8 (each cycle = 28 days)...

Chimeric antigen receptor (CAR) modified T cell therapies targeting BCMA have displayed impressive activity in the treatment of multiple myeloma. There are currently two FDA licensed products, ciltacabtagene autoleucel and idecabtagene vicleucel, for treating relapsed and refractory disease. Although correlative analyses performed by product manufacturers have been reported in clinical trials, there are limited options for reliable BCMA CAR T detection assays for physicians and researchers looking to explore it as a biomarker for clinical outcome...

Elranatamab efficacy in the single-arm, registrational MagnetisMM-3 trial (NCT04649359) was compared with that of physician's choice of treatment (PCT) for triple-class refractory multiple myeloma. MagnestisMM-3 eligibility criteria were applied to two USA-based oncology electronic health record databases, COTA and Flatiron Health (FH), to identify cohorts for this study (NCT05932290). Applied statistical techniques accounted for cohort imbalances. MagnetisMM-3 (BCMA-naive; n = 123) outcomes were compared with those from COTA (n = 239) and FH (n = 152)...

Nirogacestat (OGSIVEO™) is an oral, selective, reversible, small molecule γ-secretase inhibitor developed by SpringWorks Therapeutics, Inc. γ-Secretase is a multi-subunit protease complex that cleaves multiple transmembrane protein complexes, including Notch and membrane-bound B-cell maturation antigen (BCMA). Inhibition of γ-secretase may result in growth inhibition of tumour cells overexpressing Notch, and preservation of membrane-bound BCMA may increase target density for BCMA-targeted therapy...

B-cell maturation antigen (BCMA), expressed in plasmablasts and plasma cells, could serve as a promising therapeutic target for autoimmune diseases. We reported here chimeric antigen receptor (CAR) T cells targeting BCMA in two patients with highly relapsed and refractory myasthenia gravis (one with AChR-IgG, and one with MuSk-IgG). Both patients exhibited favorable safety profiles and persistent clinical improvements over 18 months. Reconstitution of B-cell lineages with sustained reduced pathogenic autoantibodies might underlie the therapeutic efficacy...

No abstract text is available yet for this article.

B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade ≥ 3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively)...

We designed, produced, and purified a novel IgG1-like, bispecific antibody (bsAb) directed against B-cell maturation antigen (BCMA), expressed by multiple myeloma (MM) cells, and an immune checkpoint inhibitor (ICI), PDL1, expressed in the MM microenvironment. The BCMA×PDL1 bsAb was fully characterized in vitro. BCMA×PDL1 bound specifically and simultaneously, with nM affinity, to both native membrane-bound antigens and to the recombinant soluble antigen fragments, as shown by immunophenotyping analyses and surface plasmon resonance (SPR), respectively...

Chimeric antigen receptor T-cell (CAR-T) therapy targeting B-cell maturation antigen (BCMA) has shown profound efficacy and manageable toxicity in patients with relapsed/refractory multiple myeloma (RRMM). However, determining the best course of treatment for post-CAR-T therapy relapse remains a significant challenge. We conducted a retrospective analysis of patients from the phase I LEGEND-2 study (NCT03090659) enrolled at the Xi'an site, analysing the first salvage line of therapy and outcomes in patients with RRMM who progressed after receiving LCAR-B38M CAR-T therapy...

INTRODUCTION: Despite remarkable therapeutic advances over the last two decades, which have resulted in dramatic improvements in patient survival, multiple myeloma (MM) is still considered an incurable disease. Therefore, there is a high need for new treatment strategies. Genetically engineered/redirected chimeric antigen receptor (CAR) T cells may represent the most compelling modality of immunotherapy for cancer treatment in general, and MM in particular. Indeed, unprecedented response rates have led to the recent approvals of the first two BCMA-targeted CAR T cell products idecabtagene-vicleucel ('Ide-cel') and ciltacabtagene-autoleucel ('Cilta-Cel') for the treatment of heavily pretreated MM patients...

Persistent Immune Effector Cell Associated Hematotoxicity (ICAHT) is a significant side effect of BCMA CAR T-Cell therapy in patients with relapsed multiple myeloma (MM). The use of stem cell boosts in ICAHT has been described, however studies have been limited by small patient numbers and short follow up. Herein, we report on our multi-institutional experience of ICAHT, defined by an absolute neutrophil count (ANC) of ≤ 1000, thrombocytopenia with a platelet count ≤ 50,000 or/and anemia as hemoglobin (hgb) ≤9 g/dL, in patients who received BCMA CAR T therapy, and the effects of subsequent stem cell boost on hematopoietic reconstitution and clinical outcome...