Elranatamab-bcmm receives accelerated approval by FDA for multiple myeloma

Nov 2023: Elranatamab-bcmm (Elrexfio, Pfizer, Inc.) is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager that was given accelerated approval by the Food and Drug Administration for adults with relapsed or refractory multiple myeloma who have had at least four prior lines of therapy, which included a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

In MagnetisMM-3 (NCT04649359), patients with relapsed or refractory MM who are resistant to at least one proteasome inhibitor, one immunomodulatory medication, and one anti-CD38 antibody were included in open-label, single-arm, multi-center research to assess efficacy. At enrollment, patients met the criteria set forth by the International Myeloma Working Group (IMWG) for detectable disease.

The main ways to measure how well something worked were the objective response rate (ORR) and the duration of response (DOR), which were found by an independent, blinded central review following IMWG guidelines. Ninety-seven patients who had never received BCMA-directed therapy before but had at least four prior lines of therapy—a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody—made up the primary efficacy population. Ninety-seven patients (95% CI: 47.3%, 67.7%) at the recommended dose had an ORR of 57.7%. The median DOR among responders was not reached after a follow-up of 11.1 months (95% CI: 12 months, not reached). 90.4% (95% CI: 78.4%, 95.9%) was the DOR rate at six months, and 82.3% (95% CI: 67.1%, 90.9%) at nine months.

Elranatamab-bcmm’s prescribing information includes a Boxed Warning for neurologic damage, including immune effector cell-associated neurotoxicity (ICANS), and cytokine release syndrome (CRS), which can be deadly or life-threatening. Elranatamab-bcmm was administered to patients at the prescribed dose; of them, 58% experienced CRS, 59% experienced neurologic damage, and 3.3% experienced ICANS. In 0.5% of individuals, grade 3 CRS happened, while in 7% of cases, grade 3 or 4 neurologic toxicity happened. Elranatamab-bcmm is only accessible through a restricted programme under a Risk Evaluation and Mitigation Strategy (REMS), known as the ELREXFIO REMS, due to the risks of CRS and neurologic toxicity, including ICANS.

CRS, exhaustion, injection site response, diarrhoea, upper respiratory tract infection, musculoskeletal discomfort, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia were the most frequent side effects (≥20%). Decreases in haemoglobin, neutrophils, platelets, lymphocytes, and white blood cells were the most frequent Grade 3 to 4 laboratory abnormalities (≥20%).

The first treatment dose of 76 mg on Day 8 is followed by “step-up dose 1” of 12 mg on Day 1 and “step-up dose 2” of 32 mg on Day 4. The recommended elranatamab-bcmm dosages are as follows: 76 mg weekly through Week 24. The dosage interval should change to every two weeks for patients who have taken elranatamab-bcmm for at least 24 weeks, showed partial responses, or better, and sustained responses for at least two months. Elranatamab-bcmm may be taken until the disease worsens or the level of toxicity becomes intolerable.