Real-World Elranatamab in RRMM Falls Short on Durability Despite Strong Initial Responses
Key Takeaways:
- The benefit of elranatamab in real-world settings is less durable than in trials: In this heavily pretreated, frailer population, the overall response rate (ORR) was 65% and complete response (CR) was achieved in 36% of patients. But median progression-free survival (PFS) was only 4.3 months, and median overall survival (OS) was 14.6 months, notably shorter than results reported in earlier trials.
- Prior B-cell maturation antigen (BCMA) exposure may blunt response quality, especially when recent: Patients previously treated with BCMA-directed therapy had lower odds of deep responses, and those who received elranatamab within 1 year of prior BCMA treatment had worse OS.
- Supportive care may materially affect outcomes: Infections occurred in 38% of patients, and 57% of those infected required hospitalization. The use of intravenous immunoglobulin (IVIg) was associated with longer infection-free survival and improved infection-free PFS.
A large multicenter analysis of elranatamab’s effect on RRMM shows the treatment’s effectiveness raises important questions about durability, patient selection, and supportive care in real-world practice.
The study evaluated 130 patients treated across 9 academic centers between August 2023 and March 2025. The cohort consisted of a frailer, heavily pretreated population: 91% were triple-class refractory, 49% were penta-refractory, and nearly half had prior exposure to BCMA-directed therapies.
Despite these differences, response rates were comparable to those of a prior MagnetisMM-3 trial. The ORR reached 65% with a CR of 36%. However, durability lagged significantly behind trial benchmarks. Median PFS was 4.3 months, and OS was 14.6 months, which is shorter than the 17.2- and 24.6-month medians reported in MagnetisMM-3.
Prior BCMA Exposure
Prior exposure to BCMA-targeted therapies did not significantly affect survival overall but reduced the depth of response. Patients treated with elranatamab within 1 year of prior BCMA therapy had significantly worse OS and lower odds of achieving CR. These findings show that timing is an important variable when it comes to treating RRMM with bispecific antibodies.
The authors said, “Taken together, our findings do not support broad, unselected use of elranatamab in relapsed/refractory multiple myeloma, but instead favor careful patient selection.”
Infections and Safety Profile
Out of the 1039 patients, 38% suffered infections, with more than half requiring hospitalization. IVIg supplementation was used in 46% of patients and seemed to improve infection-free PFS.
Cytokine release syndrome (CRS) events occurred in 40% of patients, which was lower than CRS events in MagnetisMM-3. On the other hand, immune effector cell-associated neurotoxicity syndrome (ICANS) was more frequent than in clinical trials, and 6.2% of patients had to be admitted to the ICU. Increased ICU utilization and inpatient stays further reflect the resource intensity of treatment in real-world settings.
Implications for Policy and Practice
The study suggests that extensive, unspecified use of elranatamab may not deliver consistent value in real-world populations. Instead, treatment should be more targeted; prioritizing patients with lower disease burden and less BCMA exposure might result in better outcomes.
As bispecific antibodies expand in RRMM, aligning coverage policies with real-world evidence and supportive care strategies will help maximize benefit while managing cost and complexity.
Reference
Portuguese AJ, Davis JA, Raza S, et al. Real-world outcomes with elranatamab in multiple myeloma: a multicenter analysis from the U.S. Multiple Myeloma Immunotherapy Consortium. Blood Cancer J. 2025;16(47). doi:10.1038/s41408-026-01477-z
