Linvoseltamab Now Under FDA Review as a Potential Treatment Option for RRMM

The FDA has accepted a Biologics License Application (BLA) for linvoseltamab for the treatment of adult patients with relapsed or refractory multiple myeloma (RRMM) who are in the fourth-line setting or patients who are in the third-line setting and are refractory to the last line of therapy.¹

Acceptance of the BLA for linvoseltamab comes after resolution of manufacturing issues raised by the FDA in a complete response letter issued to the developer of linvoseltamab in August 2024. The FDA’s concern resulted from a preapproval inspection of third-party fill/finish manufacturing facility. Considering resolution of the previous issues, the FDA has set a Prescription Drug User Fee Act target action date of July 10, 2025.^1,2

“More options for patients with myeloma is always better. The current myeloma landscape is like a game of chess. We need to know how each move affects the next move.  Having more pieces on the board allows us to keep the myeloma in check,” Joshua Richter, MD, associate professor of Medicine in The Tisch Cancer Institute, Division of Hematology and Medical Oncology and director of Multiple Myeloma at the Blavatnik Family–Chelsea Medical Center at Mount Sinai told Blood Cancers Today.

The BLA is supported by findings from the pivotal phase I/II LINKER-MM1 clinical trial (NCT03761108). In that study, treatment with 200 mg of linvoseltamab elicited a deep and durable response in patients with RRMM, according to results published in the Journal of Clinical Oncology.^1,3

“Linvoseltamab is an extremely effective bispecific antibody for the treatment of myeloma with some of the highest response rates in that setting and some of the lowest risks of CRS [cytokine release syndrome] in the class. In addition, the study has built-in scheduling for monthly dosing, making things easier and better for patients on chronic therapy,” said Dr. Richter.

A total of 117 patients with RRMM were treated in LINKER-MM1. At a median follow-up of 14.3 months, linvoseltamab at a dose of 200 mg induced an overall response rate (ORR) of 71%, with a complete response (CR) rate of 50%. The median duration of response in the 200-mg cohort was 29.4 months (95% CI, 19.2-not evaluable). Among the 104 patients treated with linvoseltamab and followed up for a median of 7.4 months, the ORR was 48% and the CR rate was 21%.³

Linvoseltamab displayed an acceptable safety profile and investigator-conducted dose optimization including intrapatient dose escalation to ensure safety. The most common any-grade adverse events in both dose cohorts were cytokine release syndrome, neutropenia, and anemia. Occurrences of any-grade immune effector cell–associated neurotoxicity syndrome were observed in 7.7% of patients, and high-grade infections occurred in 74.4%. Notably, the frequency of infections decreased over time.

An application for approval of linvoseltamab is also under review by the European Medicines Agency, and linvoseltamab may soon be a new option for patients with RRMM.

References

1. Linvoseltamab BLA accepted for FDA review for the treatment of relapsed/refractory multiple myeloma. News release. Regeneron Pharmaceutical, Inc. February 11, 2025. Accessed February 11, 2025. https://investor.regeneron.com/news-releases/news-release-details/linvoseltamab-bla-accepted-fda-review-treatment
2. Regeneron provides update on Biologics License Application for linvoseltamab. News release. Regeneron Pharmaceutical, Inc. August 20, 2024. Accessed February 11, 2025. https://investor.regeneron.com/news-releases/news-release-details/regeneron-provides-update-biologics-license-application-0
3. Bumma N, Richter J, Jagannath S, et al. Linvoseltamab for treatment of relapsed/refractory multiple myeloma. J Clin Oncol. 2024;42(22):2702-2712. doi: 1200/JCO.24.01008