FDA Approves Linvoseltamab-Gcpt for Treatment of Relapsed or Refractory Multiple Myeloma

The FDA has granted accelerated approval to linvoseltamab-gcpt (Lynozyfic; Regeneron) for the treatment of adult patients with relapsed or refractory (R/R) multiple myeloma (MM) who have received at least 4 lines of prior therapy, including with a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody, according to a news release from Regeneron. Linvoseltamab becomes the first FDA-approved BCMAxCD3 bispecific antibody that can achieve biweekly dosing at week 14 and monthly dosing if a very good partial response is observed after 24 weeks of therapy.¹

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“The FDA approval of [linvoseltamab] represents meaningful progress for the multiple myeloma community. [Linvoseltamab] demonstrated early, deep, and durable responses in heavily pretreated patients, which I saw firsthand in clinical trials,” Sundar Jagannath, MD, network director of the Center of Excellence for Multiple Myeloma at Mount Sinai in New York City and an investigator of the phase 1/2 LINKER-MM1 clinical trial, said in a news release. “[Linvoseltamab] has a convenient response-adapted dosing regimen, which provides the potential to extend time between doses. This is a significant patient-centric advancement that could help reduce treatment burden.”¹

Pivotal Trial Results Bolster Linvoseltamab’s Efficacy Profile for Approval

In the open-label, multicenter, dose-escalation and expansion phase 1/2 LINKER-MM1 trial, 282 patients with R/R MM were enrolled to investigate the safety and efficacy of linvoseltamab. The phase 1 dose-escalation portion of the trial investigated linvoseltamab’s safety, tolerability, and dose-limiting toxicities, while the phase 2 portion primarily investigated objective response rate (ORR) and key secondary end points, including duration of response (DoR), progression-free survival (PFS), minimal residual disease (MRD) negativity rate, and overall survival (OS).^1,3

The results demonstrated significant efficacy of linvoseltamab in this population. Data indicated a 70% ORR, with 45% achieving a complete response (CR) or better, as determined by an independent review committee. Furthermore, there was a 0.95-month median time to first response, while the median DoR was not reached (95% CI, 12 months–not estimable). Estimated DoR was about 89% at 9 months (95% CI, 77–95 months) and 72% at 12 months (95% CI, 54–84 months) among responders who had a median follow-up of 13 months, according to the investigators.^1,3

Positively, median PFS was not reached in the trial, with data indicating a 70% estimated PFS probability at 12 months among the cohort. This estimation was 96% among patients who experienced a CR or better, suggesting that achieving a CR induces a sustained, long-term effect for patients with R/R MM. Median OS was determined to be 31 months for all patients (95% CI, 22 months–not estimable), and median OS was not reached for patients experiencing a CR or better.³

Safety indications were generally positive, despite the appearance of cytokine release syndrome (CRS) as a treatment-emergent adverse event, which was observed in 46% of patients and occurs with many bispecific antibody treatments. Given this risk, the prescribing information for linvoseltamab contains a Boxed Warning for CRS and neurological toxicity. Furthermore, infections were reported in 74% of patients, with 36% being categorized as grade 3 or 4; in a critical observation, the severity and frequency of the infections were reduced following the 6-month point.³

Details of Approval, Including REMS Designation

Earlier this year, the FDA accepted a biologics license application (BLA) for review of linvoseltamab, constituting remarkable speed from acceptance of a BLA to full regulatory approval. Due to its safety risks, linvoseltamab stands to only be available through a Risk Evaluation and Mitigation Strategy (REMS) program, which mandates that clinics and hospitals that dispense linvoseltamab be specially certified and have immediate access to tocilizumab (Actemra; Genentech) to treat CRS.^1,4,5

The FDA recently announced the removal of REMS requirements for all currently approved BCMA-directed chimeric antigen receptor (CAR) T-cell immunotherapies, noting that their safety benefits now outweigh the possible risks of CRS or neurotoxicity. It is possible that, after more clinical trials of linvoseltamab are completed and time after its FDA approval passes, the REMS requirement for the drug will be removed as well.^1,5

Regardless of the REMS designation, the approval of linvoseltamab represents another giant leap in the MM treatment paradigm, offering patients another effective bispecific antibody treatment possibility. Importantly, the regimen includes hospitalization for safety purposes and follows an intravenous, step-up dosing infusion protocol, meaning pharmacists must be educated in dosing methods and scheduling to ensure proper administration and treatment effectiveness.¹

“Even though the number of treatment options for multiple myeloma has expanded in recent years, it remains an incurable disease with considerable unmet need, especially among patients who have undergone multiple lines of treatment,” Diane Moran, RN, MA, EdM, interim CEO and senior vice president of strategic planning at the International Myeloma Foundation, said in the news release. “The FDA approval of [linvoseltamab] is a welcome milestone.”¹

REFERENCES

1. Regeneron. Lynozyfic™ (linvoseltamab-gcpt) Receives FDA Accelerated Approval for Treatment of Relapsed or Refractory Multiple Myeloma. News Release. Released July 2, 2025. Accessed July 2, 2025. https://investor.regeneron.com/news-releases/news-release-details/lynozyfictm-linvoseltamab-gcpt-receives-fda-accelerated-approval

2. A Study to Examine the Effects of Novel Therapy Linvoseltamab in Combination With Other Cancer Treatments for Adult Patients With Multiple Myeloma That is Resistant to Current Standard of Care Treatments. National Library of Medicine. ClinicalTrials.gov Identifier: NCT05137054. Last Updated June 24, 2025. Accessed July 2, 2025. https://clinicaltrials.gov/study/nct05137054

3. James D. Phase I/II LINKER-MM1 Trial Data Show Depth of Response with Linvoseltamab for Relapsed/Refractory Multiple Myeloma. Applied Clinical Trials. Published June 17, 2024. Accessed July 2, 2025. https://www.appliedclinicaltrialsonline.com/view/trial-data-response-linvoseltamab-relapsed-refractory-multiple-myeloma

4. Regeneron. Linvoseltamab BLA Accepted for FDA Review for the Treatment of Relapsed/Refractory Multiple Myeloma. News Release. Published February 11, 2025. Accessed July 2, 2025.

5. Halpern L. FDA Removes REMS for Currently Approved BCMA-, CD19-Directed CAR T Cell Immunotherapies. Pharmacy Times. Published June 30, 2025. Accessed July 2, 2025. https://www.pharmacytimes.com/view/fda-removes-rems-for-currently-approved-bcma--cd19-directed-car-t-cell-immunotherapies