Alexander M. Lesokhin, MD, on Initial Safety Data for Elranatamab in Multiple Myeloma
Posted: Friday, July 8, 2022
Alexander M. Lesokhin, MD, of Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, discusses phase II findings from the MagnetisMM-3 trial, which tested once-weekly elranatamab, a B-cell maturation antigen (BCMA)-CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma who had received no prior BCMA-targeted treatment. This agent, with a two step–up priming regimen, appeared to be well tolerated.
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
So the MagnetisMM-3 Study was a Phase 2 evaluation of elranatamab, a BCMA CD3 bispecific antibody, in two groups of patients: those with multiple myeloma that were refractory to an IMiD, a proteasome inhibitor and an anti-C38 antibody, and had either never received prior BCMA-directed therapy or had previously received BCMA-directed antibody drug, conjugate, or CAR T cell therapy. At ASCO this year, we presented the interim analysis of the first cohort, those that had not previously received BCMA-directed treatment with data available at the time of data cut on March 23, 2022. The primary outcome of the study was overall response and safety endpoints as well as variety of other, progression-free survival, duration of response, et cetera, type of endpoints. The drug was evaluated in a two-dose step-up, 12 mg and 36 mg subcutaneously administered on day one and four, and then followed by every two week dosing with 76 mg subcutaneously weekly for the first six months and then after six months transitioned to every other week thereafter. This design was based on prior experience in both the Phase 1 MagnetisMM-1 Study and early patient experience on this study that really set the bar for reducing incidence of CRS by this two-step-up dose schedule. The patient population included in the study was 94 patients. That was presented at ASCO this year. Median age was 69. This was a heavily pretreated patient population. All were triple exposed, and a large percentage were also refractory to last line of therapy. 95% and 40% were Penta drug refractory. The disposition of patients at the time of data cut included 55% of patients that remained on treatment. Those that discontinued were largely discontinued because of progressive disease. The mean toxicities reported were hematologic. This of course is a heavily pretreated patient population. The main non-hematologic toxicities were CRS that occurred in 60% of patients. There were also infections noted in 52% of patients. This of course was a study run during the pandemic so 15% of individuals had COVID-related adverse events, and there were a variety of other upper respiratory infections as well that were noted. PJP and CMV reactivation was noted on this study. Importantly, the two-dose step-up was very effective in mitigating CRS incidence. The majority of CRS occurred on the first dose that 12 mg dose, and then with diminishing frequency thereafter with very little CRS beyond the third dose. That would be the cycle one, day eight dose. The overall response of the study at the time of median follow up of 3.7 months was 60%, and all patient subgroups were responding as of the data cut. Among those that had an objective response, almost 90% were ongoing on treatment. So I think in summary, elranatamab was quite efficacious and had a manageable safety profile in patients with triple refractory multiple myeloma. The two-step priming regimen was successful in mitigating CRS with an incidence of 59% once that two-step-up dose was used. There was a high response rate, 61%, which was observed early, and clinical benefit was seen among all subgroups. So I think the study was quite successful, and elranatamab is a therapy that will continue to be developed for multiple myeloma in additional clinical trials. Some of these studies include the MagnetisMM-5 Study, which will evaluate elranatamab as a single agent in the early relapse setting, compared with elranatamab with daratumumab or dara, pom, dex as the control alarm. An additional study is planned looking at elranatamab as a single agent among patients with newly diagnosed myeloma after transplant to evaluate elranatamab as a maintenance therapy.