Elranatamab-bcmm Granted Accelerated Approval for Multiple Myeloma
The FDA granted accelerated approval to elranatamab-bcmm (Elrexfio™, Pfizer, Inc.) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including one proteasome inhibitor, one immunomodulatory agent, and one anti-CD38 monoclonal antibody. Elranatamab-bcmm is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager.
Why it matters: "Elranatamab is a humanized bispecific antibody that targets both BCMA-expressing multiple myeloma cells and CD3-expressing T cells, with binding resulting in T-cell–mediated cytotoxicity," wrote Alexander Lesokhin, an Associate Attending Physician at Memorial Sloan Kettering Cancer Center, and colleagues, in their published abstract of the MagnetisMM-3 (NCT04649359) trial, on which accelerated approval was based. "Elranatamab preclinical studies have demonstrated antitumor activity and delayed tumor progression."
What they studied: Efficacy was measured in the phase 2, open-label, single-arm, multicenter trial in which the primary efficacy population included 97 patients with relapsed or refractory multiple myeloma who were naive to prior BCMA-directed therapy and who had previously received at least four prior lines of therapy. At enrollment, patients had measurable disease by International Myeloma Working Group (IMWG) criteria and were refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 antibody.
Patients received the recommended two step-up dose process of elranatamab-bcmm: 12 mg on Day 1, 32 mg on Day 4, 76 mg on Day 8, followed by 76 mg weekly through Week 24, administered subcutaneously. The dose interval was adjusted to every two weeks for patients who received at least 24 weeks of treatment, had achieved partial responses or better, and maintained responses for at least 2 months.
The primary end points measured were objective response rate and duration of response, as assessed by a blinded independent central review based on IMWG criteria.
What they found: Of the 97 patients in the primary efficacy population, the objective response rate with elranatamab-bcmm was 57.7%. The median duration of response was not reached within the 11.1-month median follow-up period. At six months, the median duration of response was 90.4%, and at nine months, the median was 82.3%.
Adverse events: The most common adverse events experienced in ≥20% of the treatment population were cytokine release syndrome (CRS), fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and pyrexia. The most common grade 3 to 4 laboratory abnormalities in ≥20% of the treatment population were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets.
What to know: Please refer to the prescribing information for a Boxed Warning detailing the risk for life-threatening or fatal CRS and neurologic toxicity, including immune effector cell–associated neurotoxicity (ICANS). Due to these risks, elranatamab-bcmm is only available through the restricted program called the Elrexfio™ Risk Evaluation and Mitigation Strategy (REMS).
What's next: Further analysis is ongoing and will continue to measure the safety and efficacy of elranatamab-bcmm.
Conclusion: "In patients with relapsed or refractory multiple myeloma and prior exposure to BCMA-directed therapies, elranatamab was efficacious and well tolerated; no new safety signals were observed versus the BCMA-naive population," concluded Ajay Nooka, Director of the Multiple Myeloma Program at Winship Cancer Institute of Emory University, and colleagues in their pooled analysis from the MagnetisMM studies. "Results support treatment with elranatamab in patients with relapsed/refractory multiple myeloma post–BCMA-directed therapy."
Instructions: The recommended dosage of elranatamab-bcmm is a two step-up dose process including 12 mg on Day 1, 32 mg on Day 4, 76 mg on Day 8, followed by 76 mg weekly through Week 24. The dose interval should be adjusted to every two weeks for patients who received at least 24 weeks of treatment, achieved partial responses or better, and maintained responses for at least 2 months. Treatment may be continued until disease progression or unacceptable toxicity.
For More Information
Lesokhin A, Iida S, Stevens D, et al (2021). Magnetismm-3: an open-label, multicenter, non-randomized phase 2 study of elranatamab (PF-06863135) in patients with relapsed or refractory multiple myeloma. Blood, 138(suppl_1): 1674. DOI:10.1182/blood-2021-152984
Nooka A, Lesokhin A, Mohty M, et al (2023). Efficacy and safety of elranatamab in patients with relapsed/refractory multiple myeloma (RRMM) and prior B-cell maturation antigen (BCMA)-directed therapies: A pooled analysis from MagnetisMM studies. J Clin Oncol, 41(suppl_16). Abstract 8008. DOI:10.1200/JCO.2023.41.16_suppl.8008
Clinicaltrials.gov (2023). MagnetisMM-3: Study of elranatamab (PF-06863135) monotherapy in participants with multiple myeloma who are refractory to at least one PI, one IMiD and one anti-CD38 mAb. NLM identifier: NCT04649359.
Elrexfio™ (elranatamab-bcmm) prescribing information (2023). Pfizer Inc. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761345s000lbl.pdf
US Food and Drug Administration (2023). FDA grants accelerated approval to elranatamab-bcmm for multiple myeloma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-elranatamab-bcmm-multiple-myeloma
Image credit: Dr Erhabor Osaro. Licensed under: CC BY-SA 3.0.