On July 2, 2025, the Food and Drug Administration 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 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.

Full prescribing information for linvoseltamab-gcpt will be posted on Drugs@FDA.

Efficacy and Safety

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.

Expedited Programs

The application was granted priority review. Linvoseltamab-gcpt received orphan drug designation and fast track designation. FDA expedited programs are described in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

Source: FDA