Relapsed and refractory multiple myeloma (RRMM) remains associated with poor outcomes, particularly in patients exposed or refractory to proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies. Targeting B-cell maturation antigen (BCMA) has emerged as an effective therapeutic strategy, prompting the development of bispecific antibodies that redirect T-cell cytotoxicity toward malignant plasma cells. Elranatamab is a humanized BCMA × CD3 bispecific antibody that has demonstrated clinically meaningful activity in heavily pretreated RRMM. This review summarizes and critically appraises available evidence on elranatamab, focusing on its mechanism of action, clinical efficacy, safety profile, patient-reported outcomes, and comparative positioning within the evolving BCMA-directed treatment landscape. Across studies, elranatamab has shown high response rates, durable disease control, and manageable toxicity, with predominantly low-grade cytokine release syndrome and limited neurotoxicity when administered with step-up dosing. Emerging data indicate preserved efficacy in patients previously exposed to BCMA-targeted therapies and feasibility in selected high-risk populations, including those with severe renal impairment. Nevertheless, uncertainties remain regarding optimal sequencing, long-term survival benefit, infection risk management, and mechanisms of resistance. Overall, elranatamab represents a valuable addition to the therapeutic armamentarium for RRMM. Ongoing studies and real-world experience will be critical to refine its positioning, identify patients most likely to benefit, and define its role in combination strategies.
Elranatamab in Relapsed/Refractory Multiple Myeloma: Mechanisms, Clinical Evidence, and Emerging Perspectives
Amodio, Nicola;Vigna, Ernesto;Morabito, Fortunato;Gentile, Massimo
2026-01-01
Abstract
Relapsed and refractory multiple myeloma (RRMM) remains associated with poor outcomes, particularly in patients exposed or refractory to proteasome inhibitors, immunomodulatory agents, and anti-CD38 monoclonal antibodies. Targeting B-cell maturation antigen (BCMA) has emerged as an effective therapeutic strategy, prompting the development of bispecific antibodies that redirect T-cell cytotoxicity toward malignant plasma cells. Elranatamab is a humanized BCMA × CD3 bispecific antibody that has demonstrated clinically meaningful activity in heavily pretreated RRMM. This review summarizes and critically appraises available evidence on elranatamab, focusing on its mechanism of action, clinical efficacy, safety profile, patient-reported outcomes, and comparative positioning within the evolving BCMA-directed treatment landscape. Across studies, elranatamab has shown high response rates, durable disease control, and manageable toxicity, with predominantly low-grade cytokine release syndrome and limited neurotoxicity when administered with step-up dosing. Emerging data indicate preserved efficacy in patients previously exposed to BCMA-targeted therapies and feasibility in selected high-risk populations, including those with severe renal impairment. Nevertheless, uncertainties remain regarding optimal sequencing, long-term survival benefit, infection risk management, and mechanisms of resistance. Overall, elranatamab represents a valuable addition to the therapeutic armamentarium for RRMM. Ongoing studies and real-world experience will be critical to refine its positioning, identify patients most likely to benefit, and define its role in combination strategies.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.


