Elranatamab: Durable Responses in Frail Multiple Myeloma Patients

Elranatamab Shows Promise in Real-World Multiple Myeloma Treatment, Despite Shorter Progression-Free Survival

A new analysis reveals that the immunotherapy drug elranatamab (Elrexfio) demonstrates significant activity in patients with relapsed or refractory multiple myeloma, even those with challenging health profiles, though its progression-free survival (PFS) appears numerically shorter than that of a similar therapy, teclistamab (Tecvayli). The findings, presented at the 2025 American Society of Hematology (ASH) Annual Meeting and Exposition, underscore the importance of supportive care in maximizing treatment outcomes.

Real-World Effectiveness Confirmed

The retrospective study, encompassing 130 patients treated at nine US centers between August 2023 and March 2025, assessed the effectiveness of elranatamab in a “real-world” setting – meaning outside the tightly controlled environment of clinical trials. According to presenting author Andrew J. Portuguese, MD, of Fred Hutch and the University of Washington School of Medicine, “Elranatamab retains meaningful activity in a frail, heavily pretreated real-world population.” He further emphasized that the data “reinforce its effectiveness beyond the clinical trial population and highlight areas where supportive care may improve outcomes.”

The overall response rate (ORR) with elranatamab was 65% (81 of 125 patients), with 46% achieving a very-good partial response (VGPR) or better and 36% reaching a complete response (CR) or better. These rates are comparable to those observed in the phase 3 MagnetisMM-3 trial (NCT04649359), which reported an ORR of 61%, a VGPR or better rate of 56.1%, and a CR or better rate of 35%.

Survival Outcomes and Key Predictors

While the response rates were encouraging, the median progression-free survival (PFS) was 4.27 months, significantly shorter than the 17.2 months observed in the MagnetisMM-3 trial cohort. The median overall survival (OS) was 14.6 months, compared to 24.6 months in the trial group. However, investigators noted that the patients in the real-world cohort had less favorable baseline characteristics, potentially contributing to the difference in PFS and OS.

A comparison with a French compassionate-use cohort showed similar one-year survival estimates, with OS rates of 42% versus 58%, PFS rates of 34% versus 36%, and duration of response (DOR) rates of 48% versus 50%. The median duration of response in the real-world study was 12.2 months, while it was not yet reached in the MagnetisMM-3 trial.

Several factors were identified as predictors of outcome. Higher levels of lactate dehydrogenase (LDH) were associated with worse PFS and OS, while lower hemoglobin levels correlated with poorer PFS and a reduced likelihood of achieving a complete response. Patients with an ECOG performance status of 2 or higher – indicating significant limitations in physical activity – experienced substantially worse outcomes across all measured endpoints.

Safety Profile and Management of Side Effects

The study also examined the safety profile of elranatamab in a real-world setting. Cytokine release syndrome (CRS) occurred in 39% of patients, similar to rates seen in the MagnetisMM-3 trial. However, immune-effector cell-associated neurotoxicity syndrome (ICANS) was observed in 17% of patients, a higher rate than reported in the trial.

Infections were a significant concern, occurring in 38% of patients, with 57% classified as severe. Notably, the use of intravenous immunoglobulin (IVIg) was linked to a lower risk of both treatment discontinuation and infection, with an infection-free survival hazard ratio of 0.46.

Implications for Clinical Practice

These findings suggest that elranatamab remains a valuable treatment option for patients with relapsed or refractory multiple myeloma, even in those who are heavily pretreated or have less favorable characteristics. The data highlight the importance of proactive management of side effects, particularly infections, and the potential benefit of IVIg prophylaxis. Further research is needed to identify strategies to optimize outcomes and address the factors contributing to shorter PFS in the real-world setting.

References

1. Portuguese AJ, Davis J, Raza S, et al. Real-world outcomes with elranatamab in multiple myeloma: A multi-center analysis from the United States multiple myeloma immunotherapy consortium. Blood. 2025;146(supp_1):136. doi:10.1182/blood-2025-136
2. Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023;29(9):2259-2267. doi:10.1038/s41591-023-02528-9
3. Tomasson MH, Iida S, Niesvizky R, et al. Long-term survival and safety of elranatamab in patients with relapsed or refractory multiple myeloma: Update from the MagnetisMM-3 study. Hemasphere. 2024;8(7):e136. Published 2024 Jul 24. doi:10.1002/hem3.136
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