Real-World Elranatamab Maintains Responses in Elderly, Frail R/R Multiple Myeloma

Elranatamab-bcmm (Elrexfio) demonstrated poorer progression-free survival (PFS) but greater response rates vs eclistamab-cqyv (Tecvayli) in patients with relapsed/refractory multiple myeloma according to real-world data on respective agents presented at the 2025 American Society of Hematology Annual Meeting and Exposition, though the elranatamab cohort notably had less favorable characteristics at baseline.¹

“Elranatamab retains meaningful activity in a frail, heavily pretreated real-world population,” said presenting study author Andrew J. Portuguese, MD, an assistant professor in the Clinical Research Division and a physician at Fred Hutch, and an assistant professor in the Division of Hematology and Oncology at the University of Washington School of Medicine. “Despite its limitations, elranatamab is an important addition to our therapeutic armamentarium. Our data reinforce its effectiveness beyond the clinical trial population and highlight areas where supportive care may improve outcomes.”

Efficacy Observed in the Real-World Study

The overall response rate (ORR) with elranatamab was 65% (n = 81/125), with a very-good partial response (VGPR) or better rate of 46%, and a complete response (CR) or better rate of 36%. These findings were compared with cohort A of the phase 3 MagnetisMM-3 trial (NCT04649359), which found an ORR of 61%, a VGPR or better rate of 56.1%, and a CR or better rate of 35%.^2,3

The median duration of therapy was 4.0 months in all patients, though if a patient had a VGPR or better, it was 7.9 months. Treatment was discontinued by 12% of patients due to toxicity or non-relapse mortality; users of intravenous immunoglobulin (IVIg) experienced a lower rate of discontinuation than non-users (5% vs 17%; P = .03).

With a median follow-up of 7.5 months in the presented dataset and 28.4 months in the cohort A of MagnetisMM-3 cohort, the median overall survival (OS) was 14.6 months (95% CI, 8.6-not available [NA]) vs 24.6 months (95% CI, 13.4-NA), respectively, the median PFS was 4.27 months (95% CI, 3.4-11.3) vs 17.2 months (95% CI, 9.8-NA), and the median duration of response (DOR) was 12.2 months (95% CI, 6.1-NA) vs not reached (95% CI, NA-NA).

The 1-year survival estimates were similar to what was observed in a French compassionate-use cohort, with 1-year OS rates of 42% vs 58%, respectively, 1-year PFS rates of 34% vs 36%, and 1-year DOR rates of 48% vs 50%; the median DOR was 11.0 months vs 12.2 months.⁴ The French compassionate-use cohort included 101 patients and had a median follow-up of 15.5 months.

Additionally, survival with real-world elranatamab was comparable for patients who were trial-eligible and trial-ineligible. The HR was 1.22 (95% CI, 0.57-2.62; P = .62) for OS, 1.36 (95% CI, 0.73-2.53; P = .34) for PFS, and 0.92 (95% CI, 0.36-2.35; P = .87) for DOR. The investigators also noted that an ECOG performance status of 2 was underrepresented in cohort A of MagnetisMM-3, with rates of 7% vs 24%, respectively.

Results differed for patients based on ECOG performance status. Split into groups of patients with an ECOG performance status of 0 or 1, 2, or higher than 3, the median OS was NA, NA, and 2.27 months, respectively (P = 2.6e-05); the median PFS was 6.53 months, 2.1 months, and 1.08 months (P = .002); and the median DOR was NA, 11.7 months, and 0.4 months (P = .12).

Survival outcomes based upon BCMA-naïve and BCMA-exposed status were also comparable, with a median time to prior BCMA of 15.5 months (IQR, 11.8 to 20.5). The HR for OS for patients who were BCMA-naïve vs BCMA-exposed was 0.67 (95% CI, 0.37-1.21; P = .18); 1.23 (95% CI, 0.77-1.98; P = .39) for PFS; and 0.61 (95% CI, 0.26-1.44; P = .26) for DOR.

Trial Breakdown

This analysis included 130 patients who were enrolled across 9 US centers from August 2023 to March 2025. The average set of high-risk cytogenetic abnormalities was defined as gain/amp(1q), del(17p), t(4;14), and t(14;16).

The median age was 71 years, with 57% of patients being female, 82% being White, and 48% having an ECOG performance status of 1.The median number of prior lines of therapy was 6 (IQR, 4-8), 51% received prior autologous stem cell transplantation, 42% received prior CAR T-cell therapy, and 89% were refractory to anti-CD38.

Of the patients in the analysis, 22% would have been eligible for cohort A of MagnetisMM-3.

The objectives of the retrospective analysis were to describe real-world outcomes with commercial elranatamab, identify clinical predictors of response and survival, evaluate the effect of prior BCMA therapy, and examine the impact of IVIg prophylaxis.

How Safe Is Elrantamab in Older Patients?

Regarding safety, cytokine release syndrome (CRS) occurred in 39% of patients, with 12% of events being grade 2 or higher and 2.3% being grade 3 or higher; notably, this was similar to cohort A of MagnetisMM-3. Immune-effector cell-associated neurotoxicity syndrome (ICANS) occurred in 17% of patients, with grade 2 or higher events occurring in 7.7%; the investigators noted that these rates were higher than what was observed in cohort A of MagnetisMM-3.

The median onset of CRS was 2 days, with a median duration of 1 to 2 days. Tocilizumab (Actemra) and steroids were used by 36% and 23%, respectively, and an intensive-care unit stay was needed by 6.2%.

Infections occurred in 38% of patients (n = 49), with 57% being severe, defined as requiring hospitalization or intravenous antibiotics. IVIg was received by 46% of patients and was linked with lower infection risk. Notably, most severe infections were bacterial (71%), with viral (21%) and fungal (7.1%) infections being less common.

For infection-free survival, the HR for no IVIg or IVIg was 0.46 (95% CI, 0.25-0.84; P = .013); for infection-free PFS, it was 0.58 (95% CI, 0.33-1.02; P = .058).

Predictors of Outcome

It was found that higher lactate dehydrogenase (LDH) was associated with worse PFS and OS (adjusted HR, 1.3 and 1.4 per 100 U/L; P <.001); lower hemoglobin was associated with worse PFS (aHR, 0.84; P = .034) and less likely CR (aOR, 1.4 per g/dL; P = .008); and ECOG performance status of 2 or higher was associated with less likely ORR (aOR, 0.34; P = .019).

Prior BCMA exposure was associated with a lower CR or better rate (aOR, 0.32; P = .037) and a shorter OS if less than 1 year from prior BCMA (HR, 3.66; P = .017).

Essentially, higher hemoglobin was associated with better outcomes, and higher ferritin and LDH were associated with worse outcomes.⁵

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
4. Merz M, Dima D, Hashmi H, et al. Bispecific antibodies targeting BCMA or GPRC5D are highly effective in relapsed myeloma after CAR T-cell therapy. Blood Cancer J. 2024;14(1):214. Published 2024 Dec 5. doi:10.1038/s41408-024-01197-2
5. Gauthier J, Wu QV, Gooley TA. Cubic splines to model relationships between continuous variables and outcomes: a guide for clinicians. Bone Marrow Transplant. 2020;55(4):675-680. doi:10.1038/s41409-019-0679-x