FDA grants accelerated approval to linvoseltamab for relapsed or refractory multiple myeloma in 4L+
On July 2, 2025, the Food and Drug Administration granted accelerated approval to linvoseltamab-gcpt (Lynozyfic, Regeneron Pharmaceuticals, Inc.), a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, for adults with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody.
Efficacy was evaluated in LINKER-MM1 (NCT03761108), an open-label, multi-center multi-cohort trial. The trial included patients who had previously received at least 3 prior therapies, including a PI, an IMiD, and an anti-CD38 antibody. The trial excluded patients with prior BCMA-directed bispecific antibody therapy, prior bispecific T-cell engaging therapy, or prior BCMA CAR-T cell therapy.
The efficacy population included 80 patients who had received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
Efficacy was based on objective response rate (ORR) determined by a blinded independent review committee using International Myeloma Working Group criteria. The ORR was 70% (95% CI: 59, 80). With a median follow-up of 11.3 months among responders, the estimated duration of response (DOR) was 89% (95% CI: 77, 95) at 9 months and 72% (95% CI: 54, 84) at 12 months.
The linvoseltamab-gcpt prescribing information includes a Boxed Warning for life- threatening cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). Among patients who received linvoseltamab-gcpt in the LINKER-MM1 clinical trial at the recommended dose, CRS occurred in 46% and neurologic toxicity including ICANS in 54% of patients. Grade 3 CRS occurred in less than 1% of patients and Grade 3 or 4 neurologic toxicity occurred in 8%.
Because of the risks of CRS and neurologic toxicity, including ICANS, linvoseltamab-gcpt is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), called the Lynozyfic REMS. Other warnings and precautions include infections, neutropenia, hepatotoxicity, and embryo-fetal toxicity.
Recommended Dosage
The recommended administration of intravenous linvoseltamab-gcpt includes step-up doses of 5 mg, 25 mg, and 200 mg, followed by 200 mg weekly for 10 doses, followed by 200 mg biweekly. In patients who have achieved and maintained a very good partial response or better at or after week 24 and received at least 17 doses of 200 mg, the dosing frequency is decreased to 200 mg every 4 weeks.