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BCMA in Multiple Myeloma-A Promising Key to Therapy.

ABSTRACT: Despite the discoveries of numerous agents including next generation proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. The field of myeloma treatment in refractory or relapsed patients after standard therapy entered a new era due to the B-cell maturation antigen (BMCA) targeted approach. BCMA is a member of the tumor necrosis factor receptor family with high expression in mature B-lymphocytes and plasma cells. Given the understanding of BCMA mechanism of action in MM, BCMA plays a promising role as a therapeutic target. Several clinical trials are underway to evolve the current BCMA targeted treatment concept such as antibody-drug conjugates (ADCs), bispecific T cell engagers (BITEs) and chimeric antigen receptor (CAR) T cell therapy. Current results of representative BCMA trials may close the gap of the unmet clinical need to further improve the outcome of heavily pretreated MM patients with the potency to change the paradigm in newly diagnosed and refractory MM. This comprehensive review will give an update on various BMCA targeted treatment modalities (ADCs, BITEs, CAR T cell therapy) and its existing results on efficacy and safety from preclinical and clinical trials.

SUBMITTER: Kleber M

PROVIDER: S-EPMC8472544 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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BCMA in Multiple Myeloma-A Promising Key to Therapy.

Kleber Martina M Ntanasis-Stathopoulos Ioannis I Terpos Evangelos E

Journal of clinical medicine 20210910 18

Despite the discoveries of numerous agents including next generation proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. The field of myeloma treatment in refractory or relapsed patients after standard therapy entered a new era due to the B-cell maturation antigen (BMCA) targeted approach. BCMA is a member of the tumor necrosis factor receptor family with high expression in mature B-lymphocytes and plasma cells. Given the ...[more]

PMID: 34575199

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Project description:BackgroundPreclinical studies suggest that bb2121, a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA), has potential for the treatment of multiple myeloma.MethodsIn this phase 1 study involving patients with relapsed or refractory multiple myeloma, we administered bb2121 as a single infusion at doses of 50×106, 150×106, 450×106, or 800×106 CAR-positive (CAR+) T cells in the dose-escalation phase and 150×106 to 450×106 CAR+ T cells in the expansion phase. Patients had received at least three previous lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or were refractory to both drug classes. The primary end point was safety.ResultsResults for the first 33 consecutive patients who received a bb2121 infusion are reported. The data-cutoff date was 6.2 months after the last infusion date. Hematologic toxic effects were the most common events of grade 3 or higher, including neutropenia (in 85% of the patients), leukopenia (in 58%), anemia (in 45%), and thrombocytopenia (in 45%). A total of 25 patients (76%) had cytokine release syndrome, which was of grade 1 or 2 in 23 patients (70%) and grade 3 in 2 patients (6%). Neurologic toxic effects occurred in 14 patients (42%) and were of grade 1 or 2 in 13 patients (39%). One patient (3%) had a reversible grade 4 neurologic toxic effect. The objective response rate was 85%, including 15 patients (45%) with complete responses. Six of the 15 patients who had a complete response have had a relapse. The median progression-free survival was 11.8 months (95% confidence interval, 6.2 to 17.8). All 16 patients who had a response (partial response or better) and who could be evaluated for minimal residual disease (MRD) had MRD-negative status (≤10-4 nucleated cells). CAR T-cell expansion was associated with responses, and CAR T cells persisted up to 1 year after the infusion.ConclusionsWe report the initial toxicity profile of a BCMA-directed cellular immunotherapy for patients with relapsed or refractory multiple myeloma. Antitumor activity was documented. (Funded by Bluebird Bio and Celgene; CRB-401 ClinicalTrials.gov number, NCT02658929.).

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BCMA in Multiple Myeloma-A Promising Key to Therapy.

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BCMA in Multiple Myeloma-A Promising Key to Therapy.

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