On August 14, 2023, the bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager elranatamab-bcmm was granted accelerated approval by the U.S. Food and Drug Administration (FDA) for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy (including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody).1
Supporting Efficacy Data
Approval was supported by findings in the MagnetisMM-3 trial (ClinicalTrials.gov identifier NCT04649359). In this study, 97 patients with no prior BCMA-directed therapy received subcutaneous (SC) elranatamab at step-up doses on days 1, 4, and 8, and then once weekly. After 24 weeks, the dose interval was changed to every 2 weeks in patients who achieved and maintained a partial response or better for at least 2 months.
Objective response on blinded independent central review was observed in 56 patients (57.7%, 95% confidence interval [CI] = 47.3%–67.7%), with a complete response or better in 25 patients (25.8%). At a median follow-up of 11.1 months among responders, the median duration of response was not reached (95% CI = 12 months to not reached), with 90.4% and 82.3% of responses persisting at 6 and 9 months, respectively.
KEY POINTS
- The BCMA-directed CD3 T-cell engager elranatamab-bcmm was granted accelerated approval by the FDA for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy (including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody).
- The recommended subcutaneous elranatamab dosages include a step-up dose of 12 mg on day 1, a step-up dose of 32 mg on day 4, followed by 76 mg on day 8, and then 76 mg weekly through week 24.
How It Is Used
The recommended SC elranatamab dosages follow those used in the MagnetismMM-3 trial: a step-up dose of 12 mg on day 1, a step-up dose of 32 mg on day 4, followed by 76 mg on day 8, and then 76 mg weekly through week 24. The dose interval should be changed to every 2 weeks among patients who have received at least 24 weeks of elranatamab and have achieved and maintained a partial response or better for at least 2 months.
Labeling provides information on premedication and dosage modification for adverse reactions, including cytokine-release syndrome, neurologic toxicity (eg, immune effector cell–associated neurotoxicity syndrome [ICANS]), hematologic adverse reactions, and infections.
Safety Profile
Among 183 patients who received elranatamab in MagnetisMM-3, the most common adverse events of any grade were cytokine-release syndrome (58%), fatigue (43%), injection-site reaction (37%), diarrhea (36%), upper respiratory tract infection (34%), musculoskeletal pain (34%), and pneumonia (32%). The most common grade 3 or 4 adverse events included pneumonia and sepsis. Any-grade ICANS was reported in 3.3%; grade 3 or 4 neurologic toxicity, in 7%; and grade 3 or 4 cytokine-release syndrome, in 0.5%. The most common grade 3 or 4 laboratory abnormalities were decreased lymphocytes, neutrophils, and hemoglobin. Serious adverse events were reported in 68% of patients. Adverse events led to discontinuation of treatment in 17%. Fatal adverse events occurred in 10% of patients.
Elranatamab has a boxed warning for cytokine-release syndrome and neurologic toxicity. The agent is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called ELREXFIO REMS. Elranatamab also has warnings or precautions for infections, neutropenia, hepatotoxicity, and embryofetal toxicity.
REFERENCE
1. Elrexfio (elranatamab-bcmm) injection, for subcutaneous use, prescribing information, Pfizer Inc, August 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761345s000lbl.pdf. Accessed September 12, 2023.
