ASH 2025 | Phase Ib MagnetisMM-30 trial of elranatamab with iberdomide in R/R multiple myeloma

Elranatamab is a BCMA CD3 bispecific. In the MagnetisMM-30 study, we observed a 61% response rate, 37% CR rate. And among patients that achieved a CR, the likelihood of maintaining response at 30 months was approximately 80%. And so really the depth of response matters. And so the idea here is, can we add in additional treatment that can improve the depth of response? So iberdomide is a newer generation. It’s a CELMoD, newer generation cereblon binder that can lead to enhanced T-cell activation and T-cell function. And the thought here is perhaps it will improve responses with T-cell redirecting therapy that activates T-cells. The study is designed in two parts, a dose escalation portion and a dose optimization, part two. The data presented at this meeting was the part one dose escalation portion. And the study evaluated patients that were in earlier line settings, so two to four prior therapies, IMiD and PI exposed. Two cohorts were evaluated, elotuzumab weekly with iberdomide one milligram for 21 out of 28 days, and another cohort of elotuzumab every other week, also with iberdomide one milligram, 21 out of 28 days. A total of 22 patients were enrolled across these cohorts. The follow-up time for the first cohort is approximately nine months, and it’s about five months for the second cohort. So follow-up times are relatively short, but sufficient for evaluation of safety and preliminary response assessments. Patients received the standard lenalidomide step-up dosing, 12 milligrams, followed by on day four, 32 milligrams, and then 76 milligrams was not mentioned but iberdomide was added after they completed the step-up on day 15 in both cohorts, however the actual medication was likely lenalidomide. The main safety signal of the combination was neutropenia with about 70, over 70, slightly over 75% with a grade 3, 4 neutropenia. 60% of patients received GCSF. CRS was seen at a typical rate, approximately 60% of patients. Mostly it was grade 1. None of that required discontinuation. Infections were seen in 40% of patients, very few grade three infections actually, less than 10%, which was encouraging. Patients almost uniformly received IVIG once IgG levels were less than 400. So in terms of response, the response rate across both cohorts was 95%. And actually in the dose level, it was the minus one cohort with elotuzumab every two weeks. The VGPR rate was 89%. The CR rate was 46% or 45.5%. So very encouraging response rates and fairly high depth response rates. The PFS and OS data is definitely immature and will require additional follow-up. So the take-home point here is that the combination is like superactive. Neutropenia is the main sort of adverse event, but can be managed with GCSF administration. And, you know, the dose finding study is, sorry, the dose optimization study, the part two portion of the study is ongoing with enrollment now.

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