FDA Grants Priority Review to Linvoseltamab for Relapsed/Refractory Multiple Myeloma


A biologics license application for linvoseltamab in relapsed/refractory multiple myeloma has been accepted for priority review by the FDA.



The FDA has accepted for priority review a biologics license application for linvoseltamab (REGN5458) for the treatment of adult patients with relapsed/refractory multiple myeloma who have progressed after 3 or more prior lines of therapy.1

Linvoseltamab is a bispecific antibody designed to bridge B-cell maturation antigen on multiple myeloma cells containing CD3-expressing T cells, thereby activating T cells and facilitating the killing of cancer cells.

The FDA has set a target action date of August 22, 2024.

This regulatory decision was supported by findings from the ongoing, open-label, multicenter, dose-escalation and -expansion phase 1/2 LINKER-MM1 trial (NCT03761108), which assessed linvoseltamab in patients with relapsed/refractory multiple myeloma. The latest data cutoff occurred at a median follow-up of 11 months, at which point 71% of patients who received the agent at 200 mg (n = 117) achieved an objective response per assessment by an independent review committee, including a 46% rate of complete response (CR) or better.2

Moreover, adverse effects (AE) were observed in all patients who received the agent at 200 mg and 85% of patients experienced AEs of grade 3 or higher. The most common AE was cytokine release syndrome (CRS; 46%). Among the CRS cases, 35%, 10%, and 1% were grades 1, 2, and 3, respectively. Moreover, any-grade adjudicated immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 8% of patients, grade 3 ICANS was observed in 3 patients, and no patients experienced grade 4 of higher ICANS. Any-grade infections were observed in 73% of patients, 34% of which were grade 3/4. A total of 12% of patients died because of treatment-emergent AEs during treatment or within 30 days after the last dose. Nine percent of these deaths were caused by infections.

On February 2, 2024, the European Medicines Agency accepted for review a marketing authorization application for linvoseltamab in the same indication.3

LINKER-MM1 is currently investigating linvoseltamab in 282 patients with relapsed/refractory disease. The completed phase 1 dose-escalation portion of the trial primarily evaluated the safety, tolerability, and dose-limiting toxicities associated with 9 dose levels of linvoseltamab across different administration regimens.1

The phase 2 portion of the trial is investigating the safety and antitumor activity of the agent, with objective response rate serving as the primary end point. Key secondary end points include duration of response, progression-free survival, minimal residual disease negativity rate, and overall survival.

In the phase 2 portion, patients are required to have triple-class refractory multiple myeloma or have received 3 or more prior lines of therapy. Patients received linvoseltamab via an initial step-up dosing regimen followed by the full dose of the agent. The phase 2 portion also included a response-adapted regimen, in which patients who received the agent at 200 mg every 2 weeks and achieved a very good partial response or CR could shift to receiving the agent every 4 weeks after at least 24 weeks of therapy.

The phase 3 LINKER-MM3 trial (NCT05730036) is currently enrolling and will investigate linvoseltamab vs elotuzumab (Empliciti), pomalidomide (Pomalyst), and dexamethasone in patients with relapsed/refractory multiple myeloma.1,4 Additional planned or ongoing trials with linvoseltamab include the phase 1/2 LINKER-MM4 trial (NCT05828511) in patients with treatment-naive recently diagnosed multiple myeloma, the phase 2 LINKER-SMM1 trial (NCT05955508) in patients with high-risk smoldering multiple myeloma, and the phase 2 LINKER-MGUS1 trial (NCT06140524) in patients with high-risk monoclonal gammopathy of undetermined significance.1 Furthermore, a phase 1 trial examining linvoseltamab plus a Regeneron CD38xCD28 costimulatory bispecific antibody in patients with multiple myeloma is also planned.

Since linvoseltamab is currently undergoing clinical development, its efficacy and safety have not been fully determined by any regulatory authority.


  1. Linvoseltamab BLA for treatment of relapsed/refractory multiple myeloma accepted for FDA priority review. News Release. Regeneron. February 21, 2024. Accessed February 21, 2024. https://investor.regeneron.com/news-releases/news-release-details/linvoseltamab-bla-treatment-relapsedrefractory-multiple-myeloma
  2. Updated linvoseltamab pivotal data demonstrated strong rates and depth of response in patients with heavily pre-treated multiple myeloma. News Release. Regeneron. December 7, 2023. Accessed February 21, 2024. https://investor.regeneron.com/news-releases/news-release-details/updated-linvoseltamab-pivotal-data-demonstrated-strong-rates-and
  3. Linvoseltamab receives EMA filing acceptance for treatment of relapsed/refractory multiple myeloma. News Release. Regeneron. February 2, 2024. Accessed February 21, 2024. https://investor.regeneron.com/news-releases/news-release-details/linvoseltamab-receives-ema-filing-acceptance-treatment
  4. A trial to learn how well linvoseltamab works compared to the combination of elotuzumab, pomalidomide, and dexamethasone for adult participants with relapsed/refractory multiple myeloma (LINKER-MM3). ClinicalTrials.gov. Updated February 20, 2024. Accessed February 21, 2024. https://clinicaltrials.gov/study/NCT05730036

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