ASCO 2025 | Initial results from part I of the MagnetisMM-6 trial: investigating EDR in patients with NDMM

At this ASCO I had the privilege of presenting the initial data of part one of MagnetisMM-6 that explored elranatamab in combination with daratumumab and lenalidomide in transplant-ineligible patients with multiple myeloma. This data is highly exciting because it marks the beginning of a shift of moving T-cell redirection therapy up front. There is a strong scientific rationale to this combination, combining elranatamab with daratumumab and lenalidomide effectively engages both the adaptive and the innate immune system, and this synergy allows for a robust anti-myeloma response. 

The data presented at ASCO specifically focuses on level dose G of the study, which includes elranatamab 76 milligram subcutaneously every four weeks together with a standard dose of daratumumab 1,800 milligram and lenalidomide 25 milligram. And amongst the 37 patients enrolled, median age 75, a quarter of whom were classified as frail, we saw a quite predictable and manageable safety profile. The adverse events were very much in line with the expectations of the individual drugs. Hematological toxicities occurred in around 80% of patients. Grade 3 or 4 neutropenia occurred in around 73% of patients. But grade 3 or 4 anemia and thrombocytopenia were less frequent, occurring in around 19% of patients and 11% of patients, respectively. Infections occurred in around 70% of patients, but grade 3 and 4 infections only occurred in around 19% of patients. CRS as expected occurred in around 62% of patients, all were grade 1 and 2 and there was only one case of grade 2 ICANS. 

From an efficacy perspective we saw quite an impressive response, with an overall response rate of 97.3% and 50% of these patients had a VGPR or better and 27% had a CR or better. And what’s important, is that the response was quite durable such that at a data cutoff with a median follow-up of around eight months, the vast majority of patients are still responding. 

So going forward, the randomized Phase III portion of MagnetisMM-6 is forthcoming in part two, and this will be evaluating elranatamab, daratumumab, and lenalidomide at the described schedule and dose in comparison with daratumumab, lenalidomide, and dexamethasone in transplant-ineligible or transplant-deferred patients. 

Overall, I do think that the MagnetisMM-6 is a very important study because it heralds a new era, one in which total immune therapy is brought up front, prolonging survival with the ultimate aim of helping our patients with myeloma reach their natural lifespan. And if we can do that with just one line of treatment at the outset, that would be quite transformative.

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