Linvoseltamab-gcpt Approved for Relapsed or Refractory Multiple Myeloma
Expert Perspectives · Lyn Brook · 2025-07-03
The FDA has granted accelerated approval to linvoseltamab-gcpt (Lynozyfic™, Regeneron Pharmaceuticals, Inc.), a bispecific B-cell maturation antigen (BCMA)–directed CD3 T-cell engager, for the treatment of 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.
Why This Approval Matters
The accelerated approval of linvoseltamab-gcpt introduces a novel, BCMA-directed bispecific antibody therapy for patients with relapsed or refractory multiple myeloma who have exhausted standard treatment options. This agent offers a new mechanism of action for a population with significant unmet medical need, expanding the armamentarium for clinicians managing advanced myeloma.
Breaking Down the LINKER-MM1 Trial
Efficacy was evaluated in the LINKER-MM1 trial (NCT03761108), an open-label, multicenter, multi-cohort study. Eligible patients had received at least three prior therapies, including a PI, an IMiD, and an anti-CD38 antibody, and had not previously received BCMA-directed bispecific antibody therapy, bispecific T-cell engaging therapy, or BCMA CAR-T cell therapy. Efficacy was assessed in 80 patients who had undergone a minimum of four prior lines of therapy, encompassing the specified drug categories.
The primary efficacy end point was objective response rate (ORR), as determined by a blinded independent review committee using International Myeloma Working Group criteria. Linvoseltamab-gcpt achieved an ORR of 70%. With a median follow-up of 11.3 months among responders, the duration of response (DOR) was estimated to be 89% at nine months and 72% at 12 months.
Managing Adverse Events
The prescribing information for linvoseltamab-gcpt includes a Boxed Warning for life-threatening cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS). In the LINKER-MM1 trial, CRS occurred in 46% of patients and neurologic toxicity, including ICANS, in 54%. Grade 3 CRS was reported in less than 1% of patients, while grade 3 or 4 neurologic toxicity occurred in 8%. Due to these risks, linvoseltamab-gcpt is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), known as the Lynozyfic REMS. Additional warnings and precautions include infections, neutropenia, hepatotoxicity, and embryo-fetal toxicity.
Conclusions and Future Implications
“Linvoseltamab 200 mg induced prolonged response and survival in patients with relapsed or refractory multiple myeloma, including those with difficult-to-treat refractory disease and high tumor burden, while maintaining a generally manageable safety profile,” concluded Mansi Shah, MD, a Hematologist-Oncologist at Rutgers Cancer Institute of New Jersey, and colleagues, in their subgroup analyses of the LINKER-MM1 study. “More mature safety and efficacy data with longer follow-up and including minimal residual disease data will be presented at the meeting.”
Dosing and Administration
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, then 200 mg every two weeks. For patients achieving and maintaining a very good partial response or better at or after Week 24, and who have received at least 17 doses of 200 mg, the dosing frequency may be reduced to 200 mg every four weeks.