B-Cell Maturation Antigen-Directed Immunotherapies for the Treatment of Relapsed/Refractory Multiple Myeloma: A Review of the Literature and Implications for Clinical Practice.

Abstract

Objective: To review the pharmacology, efficacy, safety, dosing and administration, and relevance to patient care and clinical practice of B-cell maturation antigen (BCMA) directed immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapy and bispecific antibodies (BsAb), for the management of relapsed/refractory multiple myeloma (RRMM).

Data sources: A literature review of PubMed (1966 to July 2024) was conducted using the keywords idecabtagene vicleucel, ciltacabtagene autoleucel, teclistamab, elranatamab, and multiple myeloma. Data was also obtained from unpublished meeting abstracts and prescribing information.

Study selection and data extraction: All relevant published articles, unpublished abstracts, and prescribing information on anti-BCMA immunotherapies for the treatment of RRMM were reviewed.

Data synthesis: Idecabtagene vicleucel and ciltacabtagene autoleucel are BCMA-directed CAR-T cell therapies that have been compared to standard of care (SOC) regimens for MM in early relapse in the phase III trials KarMMa-3 and CARTITUDE-4, respectively. Both studies demonstrated a significantly improved in response rates, depth of response, and progression-free survival compared to SOC. BsAbs teclistamab and elranatamab have been evaluated in the phase II trials MajesTEC-1 and MagnetisMM-3, respectively. Overall response rates of 63 and 61% were observed with teclistamab and elranatamab, respectively, in a population of patients with heavily pretreated RRMM.

Relevance to patient care and clinical practice in comparison with existing drugs: BCMA-directed immunotherapies have demonstrated efficacy in the treatment of RRMM. Safety issues with BCMA-directed immunotherapies include cytokine release syndrome, neurotoxicity, infections, and cytopenias. Operational challenges and issues with access to care exist with these therapies as they may be limited to institutions with the infrastructure to safely administer and monitor patients for toxicities.

Conclusion: BCMA-directed immunotherapies represent an important advancement in the management of RRMM and have significantly added to the available treatment options for this disease.