Among patients with relapsed/refractory multiple myeloma, a central analysis of real-world Elrexfio (elranatamab-bcmm) was associated with shorter times until disease progression, or progression-free survival (PFS), but higher rates of response when compared with real-world use of Tecvayli (teclistamab-cqyv), while patients in the Elrexfio cohort had less favorable baseline characteristics, study findings have shown.
Findings were presented at the 2025 American Society of Hematology Annual Meeting and Exposition.
“[Elrexfio] retains meaningful activity in a frail, heavily pretreated real-world population,” said presenting study author Dr. Andrew J. Portuguese, 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, [Elrexfio] 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.”
Glossary
Progression-Free Survival (PFS): The length of time during and after treatment that a person lives with cancer without the disease getting worse.
Overall Response Rate (ORR): The percentage of people whose cancer shrinks or disappears after treatment.
Overall Survival (OS): The length of time from diagnosis or the start of treatment that patients are still alive, no matter what happens to the cancer.
ECOG Performance Status: A scale doctors use to describe how well a person can carry out daily activities. It ranges from 0 (fully active) to 5 (deceased) and helps guide treatment decisions.
Cytokine Release Syndrome (CRS): A possible side effect of some immune-based treatments. It happens when the immune system becomes overly active and releases many signaling proteins (cytokines), causing symptoms like fever, fatigue and low blood pressure. CRS can range from mild to serious but is treatable.
Immune-Effector Cell–Associated Neurotoxicity Syndrome (ICANS): A type of brain- and nerve-related side effect that can occur after treatments like CAR-T cell therapy. Symptoms may include confusion, trouble finding words, tremors or sleepiness. Doctors monitor patients closely and have treatments to manage ICANS.
Efficacy Observed in the Real-World Study
The overall response rate (ORR) with Elrexfio was 65% (81 of 125 patients), 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, 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 four 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% versus 17%).
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 versus 24.6 months, respectively, the median PFS was 4.27 months versus 17.2 months and the median duration of response (DOR) was 12.2 months versus not reached.
The one-year survival estimates were similar to what was observed in a French compassionate-use cohort, with one-year OS rates of 42% versus 58%, respectively, one-year PFS rates of 34% versus 36% and one-year DOR rates of 48% versus 50%; the median DOR was 11 months versus 12.2 months. The French compassionate-use cohort included 101 patients and had a median follow-up of 15.5 months.
Additionally, survival with real-world Elrexfio was comparable for patients who were trial-eligible and trial-ineligible.
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 not available, not available and 2.27 months, respectively; the median PFS was 6.53 months, 2.1 months and 1.08 months; and the median DOR was not available, 11.7 months and 0.4 months.
Survival outcomes based upon BCMA-naïve and BCMA-exposed status were also comparable.
Trial Breakdown
This analysis included 130 patients who were enrolled across nine U.S. centers from August 2023 to March 2025. 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 six, 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.
Safety
Regarding safety, cytokine release syndrome (CRS) occurred in 39% of patients, with 12% of events being grade 2 (moderate) or higher and 2.3% being grade 3 (severe) 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 two days, with a median duration of one to two days. Actemra (tocilizumab) 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, 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.
Predictors of Outcome
It was found that higher lactate dehydrogenase (LDH) was associated with worse PFS and OS; lower hemoglobin was associated with worse PFS and less likely CR and ECOG performance status of 2 or higher was associated with less likely ORR. Prior BCMA exposure was associated with a lower CR or better rate and a shorter OS if less than one year from prior BCMA. Essentially, higher hemoglobin was associated with better outcomes, and higher ferritin and LDH were associated with worse outcomes.
Reference
- “Real-world outcomes with elranatamab in multiple myeloma: A multi-center analysis from the United States multiple myeloma immunotherapy consortium” by Dr. Andrew J. Portuguese et al., Blood.
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