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Data with elranatamab-bcmm (Elrexfio) plus daratumumab (Darzalex) and lenalidomide (Revlimid) showed the combination to have a manageable safety profile and induce early responses in patients with transplant-ineligible newly diagnosed multiple myeloma, according to Meletios A. Dimopoulos, MD.
Data from part 1 of the phase 3 MagnetisMM-6 trial (NCT05623020) were presented at the 2025 EHA Congress and showed that among patients with who received elranatamab at 76 mg every 4 weeks plus daratumumab at 1800 mg and lenalidomide at 25 mg in 28-day cycles (n = 37), the safety profile of the combination was consistent with the known safety profiles of the individual agents. The most frequently reported adverse effects (AEs) were hematologic AEs (any-grade, 83.8%; grade 3/4, 78.4%), infections (70.3%; 18.9%), and cytokine release syndrome (CRS; 62.2%; 0%). Additionally, only 1 case of grade 2 immune effector cell–associated neurotoxicity syndrome was reported.
Regarding efficacy, at a data cutoff of April 1, 2025, and a median follow-up of 7.9 months (range, 1.2-9.5), the confirmed investigator-assessed overall response rate was 97.3% (95% CI, 85.8%-99.9%) and included a very good partial response (VGPR) or better rate of 94.6% and a complete response (CR) or better rate of 27.0%. Notably, the stringent CR rate was 8.1%, and the PR rate was 2.7%. The median time to response was 1.5 months (range, 0.3-4.2).
“We expect this [overall response] percentage to increase over time, because the follow-up for the treated patients is relatively short,” Dimopoulos said in an interview with OncLive®.
In the interview, Dimopoulos discussed the rationale for investigating this combination in newly diagnosed, transplant-ineligible patients, efficacy and safety data that were presented at the meeting, and where future research with elranatamab in myeloma may be headed.
Dimopoulos is a professor and chairman of the Department of Clinical Therapeutics at the National and Kapodistrian University of Athens School of Medicine in Athens, Greece.
OncLive: What was the rationale for conducting this research?
Dimopoulos: Bispecific monoclonal antibodies, particularly elranatamab, have significant activity in patients with advanced, heavily pretreated myeloma. It made sense to evaluate these agents earlier in the course of the disease. Elranatamab has been evaluated in the context of the MagnetisMM-6 study in combination with lenalidomide and daratumumab to find the best dose to move to a prospective randomized study. Different time intervals of administration of elranatamab were evaluated.
What were the key efficacy findings?
[At the 2025 EHA Congress], I presented the [data from] dose level G, which included [patients who received] elranatamab at a dose of 76 mg every 4 weeks with daratumumab and lenalidomide given at standard doses. In this cohort, we have treated a relatively large number of patients, and we’re happy to see that the VGPR or better rate was 94.6%, with many patients achieving CR.
What is the safety profile of elranatamab plus daratumumab and lenalidomide?
The tolerability of the combination is acceptable. We saw CRS, which was grade 1 almost always. With the regular use of immunoglobulin, we could significantly reduce the severity and incidence of severe infections.
What are the next steps for this research?
We have now the appropriate dose to proceed to the next step, which will be to compare this combination of elranatamab plus daratumumab and lenalidomide to the standard of care, which is lenalidomide plus daratumumab and dexamethasone, for newly diagnosed, symptomatic, previously untreated, older patients with myeloma who are not eligible or not willing to proceed to high-dose therapy.
Reference
- Dimopoulos MA, Pour L, Grosicki S, et al. Elranatamab in combination with daratumumab and lenalidomide (EDR) in patients with newly diagnosed multiple myeloma (NDMM) not eligible for transplant: initial results from MagnetisMM-6 part 1. Presented at: 2025 EHA Congress. June 12-15, 2025; Milan, Italy. Abstract S206.