Elranatamab-bcmm (Elrexfio) improved progression-free survival in a Phase 3 trial of relapsed or refractory multiple myeloma after at least 1 prior therapy.
Elranatamab (Elrexfio; Pfizer) achieved the primary endpoint of progression-free survival (PFS) at a prespecified interim analysis of the Phase 3 MagnetisMM-5 trial in adults with relapsed or refractory multiple myeloma who had received at least 1 prior line of therapy.1
The update is notable because the study moves the B-cell maturation antigen (BCMA)–CD3 bispecific antibody into an earlier-line setting than its current US accelerated approval, where elranatamab is indicated after at least 4 prior lines of therapy.2
“Effective intervention earlier in the course of disease represents a critical opportunity to improve outcomes for people living with multiple myeloma,” Jeff Legos, MD, chief oncology officer at Pfizer, said in the company announcement.1
Full efficacy data, including median progression-free survival and hazard ratio, were not disclosed in the press release, and overall survival remains immature.
Elranatamab was designed to link to BCMA, which is highly expressed on the surface of MM cells. The CD3 receptor on the surface of T-cells then connects and activates them to kill myeloma cells. The binding affinity of elranatamab for BCMA and CD3 was developed to enduce potent T-cell mediated anti-myeloma activity.3
MagnetisMM-5 is an open-label, multicenter, randomized study comparing subcutaneous elranatamab monotherapy with daratumumab, pomalidomide, and dexamethasone in 497 patients across 26 countries.
Eligible patients had relapsed or refractory disease after at least 1 prior line of therapy, including lenalidomide and a proteasome inhibitor. According to Pfizer, elranatamab produced a statistically significant improvement in PFS as per blinded independent central review, and the result exceeded the trial’s prespecified interim efficacy threshold.1 The company also stated that “most Elrexfio-treated patients” remained progression-free at the time of the analysis.1
The safety profile was consistent with prior experience and without new safety signals. That finding is relevant given the known toxic effects associated with BCMA-directed bispecific antibodies, particularly cytokine release syndrome, neurologic toxic effects, infections, and cytopenias.2
In the US label, elranatamab carries a boxed warning for cytokine release syndrome and neurologic toxicity and is available only through a Risk Evaluation and Mitigation Strategy program.2
Multiple myeloma remains incurable despite substantial therapeutic advances, and relapse after frontline and subsequent therapy is expected for most patients.4 Treatment selection in relapsed disease is increasingly shaped by prior exposure to lenalidomide and anti-CD38 antibodies, fitness, pace of relapse, and access to cellular therapy or bispecific antibodies.4,5
A positive randomized signal against daratumumab, pomalidomide, and dexamethasone may therefore be clinically relevant if confirmed in full presentation, particularly for patients with double-class–exposed disease who are not candidates for chimeric antigen receptor T-cell therapy or who need an off-the-shelf option.
Elranatamab is a subcutaneous bispecific antibody that binds BCMA on myeloma cells and CD3 on T cells, redirecting T-cell cytotoxicity. In the Phase 2
The FDA granted accelerated approval in 2023 for adults with relapsed or refractory disease after at least 4 prior lines, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.2 The European Union granted conditional marketing authorization in a somewhat earlier postexposure setting, according to the company.1
The trial is continuing, with overall survival as a key secondary endpoint. Pfizer said the data will be discussed with global regulators and submitted for presentation at a future medical meeting.
Another ongoing Phase 3 study, MagnetisMM-32, is evaluating elranatamab in patients previously treated with frontline daratumumab, reflecting the growing need to define sequencing as anti-CD38 use shifts earlier in the disease course.1
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