FDA Grants Elranatamab Accelerated Approval for Relapsed or Refractory Multiple Myeloma

FDA Grants Elranatamab Accelerated Approval for Relapsed or Refractory Multiple Myeloma

The FDA has granted accelerated approval to elranatamab-bcmm (Elrexfio) to treat adults with relapsed or refractory multiple myeloma (RRMM) who have already undergone 4 prior lines of treatment, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Elranatamab is a BCMA-CD3-directed bispecific antibody immunotherapy that is delivered subcutaneously. The agent binds to the BCMA on myeloma cells and the CD3 on T cells, bringing them together, and prompting the T cells to kill the myeloma cells. According to the manufacturers, this is the first BCMA-directed therapy approved for once-every-other-week dosing after 24 weeks of weekly therapy, which is anticipated to translate into less time at the clinic and greater long-term treatment tolerability.

The decision was supported by findings from the phase 2 MagnetisMM-3 trial (NCT04649359), a single-arm trial which demonstrated that patients with heavily treated RRMM achieved meaningful responses following treatment with elranatamab as their first BCMA-directed therapy.

For patients who had already undergone treatment with at least 4 lines of therapy (n = 97), the overall response rate with elranatamab was 58%, and it is estimated that 82% of responders maintained their response for at least 9 months.

Read more: Elizabeth Aronson, MSN, FNP-BCN, OCN, discusses how the recent approvals of elranatamab and talquetamab are changing the treatment landscape for patients with multiple myeloma.

“Accessibility is key to unlocking the potential impact of new treatment options. Unfortunately, novel therapies for triple-class-exposed multiple myeloma can be out of reach for medically underserved populations,” Jenny Ahlstrom, founder and chief executive officer of the HealthTree Foundation for Multiple Myeloma, stated in the press release. “With the approval of [elranatamab], patients have a new off-the-shelf treatment option that can be delivered on an ongoing basis in community clinics, where the majority of patients with multiple myeloma receive their care.”

Data from the MagnetisMM-3 cohort B (n = 64) is also included on the label, this dataset includes 63 patients who had received 4 prior lines of therapy, including a BCMA-directed therapy (CAR-T or antibody-drug conjugate). At a median follow-up of 10.2 months, the overall response rate for these patients was 33%. An estimated 84% of responders continued to respond for at least 9 months.

Of note, the prescribing label lists a boxed warning for cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome. Because of this risk, the agent is to be administered via a step-up-dosing regimen, and patients should receive pretreatment with acetaminophen, dexamethasone, and diphenhydramine. In addition, patients should be admitted for the 48 hours following their first step-up dose (12 mg) and for 24 hours following their second step-up dose (32 mg).

The label also includes warnings for infections, neutropenia, hepatotoxicity, and embryo-fetal toxicity.

In the trial, the following adverse events were reported by at least 20% of patients: CRS, fatigue, injection site reaction, diarrhea, upper respiratory tract infection, musculoskeletal pain, pneumonia, decreased appetite, rash, cough, nausea, and fever.

Moreover, the most common grade 3 or 4 laboratory abnormalities (reported by 20% of patients or more) were decreased lymphocytes, decreased neutrophils, decreased hemoglobin, decreased white blood cells, and decreased platelets.

Continued approval for this indication is contingent upon verification of clinical benefit in 1 or more confirmatory trials, according to Pfizer.

“Most multiple myeloma patients will experience relapse or resistance of their disease to treatment, often facing increased symptom burden and lowering their chance of surviving longer with each attempted line of therapy,” MagnetisMM clinical trial investigator, Ajay Nooka, MD, MPH, director of the Multiple Myeloma Program at Winship Cancer Institute of Emory University, added in the press release. “By offering durable clinical response with an established safety profile and the convenience of subcutaneous administration, [elranatamab] provides a much-needed new option for heavily pre-treated multiple myeloma patients who are struggling with relapsed myeloma.”

Reference

Pfizer’s ELREXFIO™ receives U.S. FDA accelerated approval for relapsed or refractory multiple myeloma. Pfizer. Press release. August 14, 2023. Accessed August 14, 2023. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-elrexfiotm-receives-us-fda-accelerated-approval