FDA Alert

FDA Grants Accelerated Approval to Linvoseltamab-gcpt for Heavily Pretreated Multiple Myeloma

Edited by:
Kate Young

Key Highlights

  • Linvoseltamab-gcpt demonstrated a 70 percent objective response rate with durable responses.
  • The therapy carries a Boxed Warning for cytokine release syndrome and neurologic toxicity, including ICANS, and is available only through the Lynozyfic REMS program due to its significant safety risks.

On July 2, 2025, the FDA granted accelerated approval to linvoseltamab-gcpt, a bispecific B-cell maturation antigen (BCMA)–directed CD3 T-cell engager, for adults with relapsed or refractory multiple myeloma previously treated with ≥4 lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. According to the agency, “the application was granted priority review,” reflecting the significant unmet need in this population.

Approval was supported by efficacy results from LINKER-MM1 (NCT03761108), an open-label, multicenter, multi-cohort trial enrolling patients with prior exposure to a proteasome inhibitor, immunomodulatory agent, and anti-CD38 antibody. The efficacy population included 80 patients who had received ≥4 prior treatment lines. Objective response rate (ORR), assessed by blinded independent review using International Myeloma Working Group criteria, was 70% (95% CI, 59–80). With a median follow-up of 11.3 months among responders, estimated duration of response (DOR) was 89% (95% CI, 77–95) at 9 months and 72% (95% CI, 54–84) at 12 months.

The prescribing information contains a Boxed Warning for life-threatening cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell–associated neurotoxicity syndrome (ICANS). Among patients receiving the recommended dose, CRS occurred in 46% and neurologic toxicity, including ICANS, in 54%. Grade 3 CRS occurred in <1%, and grade 3–4 neurologic toxicity occurred in 8%. Additional warnings include infections, neutropenia, hepatotoxicity, and embryo-fetal toxicity. Due to these risks, linvoseltamab-gcpt is available only through the Lynozyfic REMS program.

Recommended administration includes intravenous step-up dosing (5 mg, 25 mg, 200 mg), followed by 200 mg weekly for 10 doses, then 200 mg biweekly. For patients achieving and maintaining very good partial response or better at or after week 24, dosing decreases to every 4 weeks after ≥17 doses.

Reference:
U.S. Food and Drug Administration. FDA grants accelerated approval to linvoseltamab-gcpt for relapsed or refractory multiple myeloma. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-linvoseltamab-gcpt-relapsed-or-refractory-multiple-myeloma. Published July 2, 2025. Accessed Dec. 9, 2025