Multiple myeloma is the second most common blood cancer diagnosis, after non-Hodgkin lymphoma, in the US. Immunotherapy is a promising and innovative approach for myeloma treatment. It involves using monoclonal antibodies, CAR-T cells, or bispecific antibodies to boost the immune system’s ability to fight the cancer cells. These therapies have shown remarkable results in patients who have failed other treatments. However, there is still room for improvement, as some responses are not lasting. 

At EHA 2025, Pfizer presented the Phase III results of ELREXFIO + Daratumumab + Lenalidomide. As of the April 1, 2025 data cutoff, with a median follow-up of 7.9 months, the confirmed investigator-assessed objective response rate (ORR) was 97.3%. A very good Partial Response or better was achieved in 94.6% of patients, while 27% reached a Complete Response (CR) or better. Partial responses were seen in 2.7% of patients, with a median time to response of 1.5 months. 

The most common treatment-emergent adverse events were neutropenia, Cytokine Release Syndrome (CRS), fever, and anemia. Grade 3 or higher adverse events included neutropenia, anemia, thrombocytopenia, and fatigue.

KOL insights

“MagnetisMM-6 trial showed early and promising efficacy with 36 out of 37 patients having responded, and responses are expected to deepen further with longer follow-up.” – Expert Opinion

Conclusion

The multiple myeloma treatment landscape is evolving with the rise of monoclonal antibodies being used in newly-diagnosed patients. DARZALEX's position is strong, in comparison to its competitors in the market.

TECVAYLI and ELREXFIO, two BCMA/CD3-targeted bispecific antibodies, and TALVEY target GPRC5D have received FDA approval for the treatment of patients with relapsed or refractory multiple myeloma, have better activity in terms of both Progression-free Survival (PFS) and duration of response when compared to existing standards of treatment, such as POMALYST/dexamethasone. 

ELREXFIO is a subcutaneously delivered B-cell Maturation Antigen (BCMA)-CD3-directed bispecific antibody immunotherapy that binds to BCMA on myeloma cells and CD3 on T-cells, activating the T cells to kill myeloma cells. In August 2023, Pfizer announced that the US FDA granted accelerated approval to ELREXFIO for the treatment of adult patients with RRMM who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. The therapy provides the advantage of shifting to biweekly administration after an initial period of weekly treatment. While other BCMA-targeted bispecifics like TECVAYLI also show comparable efficacy, they may require weekly dosing throughout maintenance. This difference in dosing frequency could potentially lead to a more convenient treatment experience for patients on ELREXFIO.