ELREXFIO (elranatamab-bcmm) Approved By FDA
This exciting new bispecific antibody is now available to patients in the clinical setting
By Dr. Joseph Mikhael, IMF Chief Medical Officer
On August 14, 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval to Elrexfio™ (elranatamab-bcmm), a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, for adult patients with relapsed or refractory myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
The term “bispecific” means that the drug has 2 “arms,” with one arm attaching to the myeloma cell through the BCMA target on the cell surface and the other arm attaching to and activating a local T cell to destroy the myeloma cell. (CRS, a type of reaction that the immune system has when T cells are activated), hematologic-related events (low blood counts), and infections. CRS is the most frequent side effect observed with T-cell therapies, but the incidence and severity of CRS are lower with bispecific antibodies than with CAR T-cell therapy.
Response rates
On August 15, the journal Nature Medicine published a manuscript by Dr. Alexander M. Lesokhin and colleagues with the clinical trial results from the phase II MagnetisMM-3 study. Elrexfio was shown to induce deep and durable responses with a manageable safety profile.
Heavily pretreated patients with relapsed or refractory myeloma, a high number of whom had poor prognostic features at baseline, were treated with Elrexfio by subcutaneous (SQ, under the skin) injections at a dose of 76 mg once-weekly after a step-up priming dose regimen of 12 mg followed by 32 mg during the first week of treatment. After 6 cycles, persistent responders were switched to biweekly dosing (every 2 weeks). Patients in cohort A, who had not received prior BCMA-directed therapy, had an overall response rate (ORR) of 61%.
A complete response (CR) was achieved by 35% or more patients, 50 patients were switched to biweekly dosing, and 40 patients improved or maintained their response for at least 6 months. With a median follow-up of 14.7 months, median duration of response (DOR), progression-free survival (PFS) and overall survival (OS) have not been reached. Fifteen-month rates were 71.5%, 50.9% and 56.7%, respectively. The results reported from the phase II study are consistent with results reported from the phase I MagnetisMM-1 study.
Common side effects
The most common treatment emergent adverse events (TEAEs) that emerged during treatment, having been absent before treatment, or events that worsened relative to the pretreatment state that were reported in MagnetisMM-3 study were cytokine release syndrome (CRS, a type of reaction that the immune system has when T cells are activated), hematologic-related events (low blood counts), and infections. CRS is the most frequent side effect observed with T-cell therapies, but the incidence and severity of CRS are lower with bispecific antibodies than with CAR T-cell therapy.
The toxicity criteria adopted in the United States by the National Cancer Institute (NCI) for cancer clinical trials includes Grade 0 (no symptoms), Grade 1 (mild symptoms), Grade 2 (moderate symptoms), Grade 3 (symptoms requiring treatment), and Grade 4 (symptoms requiring urgent intervention). Results from the phase II study presented in parentheses below are written as “any Grade, Grade 3–4.” Side effects included infections (69.9%, 39.8%), CRS (57.7%, 0%), anemia (48.8%, 37.4%), and neutropenia (48.8%, 48.8%). Side effects decreased with biweekly dosing, with Grade 3–4 adverse events decreasing from 58.6% to 46.6%. Biweekly dosing of Elrexfio may improve safety without compromising efficacy.
All treatment centers that provide Elrexfio must adhere to a Risk Evaluation and Mitigation Strategy (REMS) program that monitors the risks of treatments.
In conclusion
Myeloma patients now have another new and important treatment option. Each new drug brings with it the potential to further help in our goal to cure myeloma. The high response rate with Elrexfio could benefit many heavily pretreated patients. This is very exciting for the myeloma community!
See the Spring 2022 edition Myeloma Today to read Dr. Mikhael’s article on bispecific antibodies and contact the IMF InfoLine with your myeloma-related questions and concerns. Phone lines are open 9 a.m. to 4 p.m. (Pacific) Monday through Friday at 1.800.452.CURE in the US and Canada and 1.818.487.7455 worldwide. You can also email [email protected] to submit your query electronically.
(This article was published in the 2023 Fall Edition of the IMF's quarterly publication, Myeloma Today. Read the full publication here.)