FDA Grants Elratamab Accelerated Approval for Relapsed or Refractory Multiple Myeloma

The FDA has granted accelerated approval for elratamab-bcmm (Elrexfio) to treat adults with relapsed or refractory multiple myeloma (RRMM) who have been on 4 previous lines of treatment, including proteasome inhibitors, immunomodulatory agents, and monoclonal anti-CD38 antibodies.

Elratamab is a BCMA-CD3 directed bispecific antibody immunotherapy that is administered subcutaneously. The agents bind to BCMA on myeloma cells and CD3 on T cells, sticking them together, and inducing T cells to kill myeloma cells. According to the manufacturer, this is the first BCMA-directed therapy approved for weekly dosing after 24 weeks of weekly therapy, which is expected to reduce time in the clinic and greater tolerability of long-term treatment.

This decision is supported by findings from the phase 2 trial of MagnetisMM-3 (NCT04649359), a one-arm trial which showed that patients with heavily treated RRMM achieved a meaningful response after treatment with elratamab as their first BCMA-directed therapy.

For patients already on treatment with at least 4 lines of therapy (n = 97), the overall response rate to elratamab was 58%, and an estimated 82% of responders maintained their response for at least 9 months.

“Accessibility is the key to unlocking the potential impact of new treatment options. Unfortunately, new therapies for grade three-exposed multiple myeloma could be beyond the reach of medically underserved populations,” Jenny Ahlstrom, founder and CEO of the HealthTree Foundation for Multiple Myeloma, stated in a press release. “With the approval of [elranatamab]patients have new treatment options that can be provided on an ongoing basis in community clinics, where the majority of patients with multiple myeloma receive their care.”

Data from the MagneticsMM-3 B cohort (n = 64) were also included on the label, this data set included 63 patients who had received 4 previous lines of therapy, including BCMA-directed therapy (CAR-T or drug-antibody conjugate). At a median follow-up of 10.2 months, the overall response rate for these patients was 33%. It is estimated that 84% of respondents continue to respond for at least 9 months.

Of note, prescription labels include boxed warnings for cytokine release syndrome (CRS) and neurological toxicity, including immune effector cell-associated neurotoxicity syndrome. Because of this risk, the agents are administered via a stepwise dosing regimen, and patients should receive initial treatment with acetaminophen, dexamethasone, and diphenhydramine. In addition, patients should be treated for 48 hours after their first step-up dose (12 mg) and for 24 hours after their second step-up dose (32 mg).

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

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

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

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

“The vast majority of multiple myeloma patients will experience a recurrence of their disease or resistance to treatment, often facing an increased symptom burden and lowering their chances of survival longer with each course of therapy tried,” MagnetisMM clinical trial investigator Ajay Nooka, MD, MPH, director of the Multiple Myeloma Program at the Winship Cancer Institute of Emory University, added in a press release. “By offering a durable clinical response with an established safety profile and the convenience of subcutaneous administration, [elranatamab] provide a much-needed new option for pre-treated multiple myeloma patients battling relapsed myeloma.”

Reference

ELREXFIO™ Pfizer receives expedited US FDA approval for relapsed or refractory multiple myeloma. Pfizer. Pers conference. 14 August 2023. Accessed 14 August 2023. https://www.pfizer.com/news/press-release/press-release-detail/pfizers-elrexfiotm-receives-us-fda-accelerated-approval