ASH 2025 | Initial results from MagnetisMM-30: elranatamab plus iberdomide in RRMM

I’m excited to share the initial report of safety and efficacy from the MagnetisMM-30 trial that combined elranatamab with iberdomide in patients with relapsed/refractory multiple myeloma. So, elranatamab is an approved BCMA CD3 bispecific antibody that was based on the Phase II MagnetisMM-3 study. In that study, the overall response rate was about 60% and complete remission rate was about 37%. Now, iberdomide itself is a novel agent. It’s an oral CELMoD, which traditionally works better than the immunomodulatory agent. It works directly by killing the cancer and also because it can activate the T-cells, increase T-cell proliferation and also T-cell engagement, it may also improve the T-cell fitness. So those two groups of drugs have complementary mechanisms of action, therefore it’s supporting the scientific reason to combine them, particularly to improve efficacy in relapsed myeloma. So the study itself has two parts. I’m reporting the data from the part one, which is a dose escalation part. The idea is to define the dose-limiting toxicity and also to define the dose to use in the part two. Patients in the study were those with relapsed/refractory myeloma. They would have needed to receive at least one prior line of therapy, including PI, IMiDs, and/or CD38 antibody. They also have to be BCMA naive. Patients all receive step-up dosing of elranatamab, standard, according to the approval package insert, and then they start the combination drug. The dose level one used elranatamab, 76 milligrams of elranatamab weekly, and iberdomide dose was a one milligram oral agent, 21 days, followed by seven days break. We also have the dose level minus one, which was created based on the side effect profile from the dose level one, and that dose level has elranatamab delivered at every other week rather than weekly. The overall objective or the primary objective is the dose-limiting toxicity, but we also collect correlative data, including the immunogenicity, pharmacokinetics, as well as the overall response rate, the time to events, and so on. So today, 22 patients were enrolled to the study, and the average age, classic myeloma, 68 years of age, quite heavily pre-treated. 50% were triple-class refractory already. They do include 18% of patients with extramedullary disease and also 40% with high-risk cytogenetics. Everybody got started on the dose level one, and the DLT though, there are four events that were observed, and they relate to neutropenia mostly. So in dose level minus one, we also observed some of the DLT, and that again was one grade three for neutropenia, and then there is one grade four neutropenia. Otherwise the side effect profile is actually quite what we would expect from both agents. CRS, ICANS rate were actually comparable with elra experience. The primary adverse event that’s grade three, four were hematological, your neutropenia, anemia, lymphopenia. Otherwise, the non-hematological side effects were quite minor, the CRS, some loss of appetite, some GI side effects were reported. Now, the exciting part is the efficacy. The overall response at the time of about 7.8 months of follow-up is already 95.5%. We know that with this kind of agents, you do see early response, but it continues to deepen over time. So we’re excited that we’re already seeing that depth of remission early on. And the response stands all across both dose levels. It also seemed to work equally well in people with high-risk cytogenetics. 40-some percent of folks had high risk disease and they still had overall response rate that was really that 88% and more. So at the end of the day, we’re combining agents that have complementary actions and hope for a synergy. And I think today, this initial result is showing that this regimen is very promising, the side effects are manageable. In the second part of the study, it will expand to larger patient cohort with also two different dose schedule optimization. And I’m hoping that this would also be a group where we get to do correlative studies to understand the T-cell profile and also its effect on the tumor.

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