CHMP Recommends Linvoseltamab for Approval in Heavily Pretreated R/R Multiple Myeloma

Despite prior relapses, 200 mg of linvoseltamab elicited complete responses or better in 49.6% of patients with relapsed/refractory multiple myeloma.

Linvoseltamab has been recommended for approval by the Committee for Medicinal Products for Human Use (CHMP) for the treatment of adult patients with relapsed/refractory multiple myeloma who received at least 3 prior therapies including a proteasome inhibitor, and immunomodulatory agent, and an anti-CD38 monoclonal antibody and demonstrated progression on the final therapy, a press release from the developer, Regeneron, stated.¹

No date was given for the pending approval, but the European Commission is anticipated to make a decision in the coming months.

Previously, in February 2025, the FDA accepted for review a biologics license application for linvoseltamab in adult patients with pretreated relapsed/refractory multiple myeloma with a target action date of July 10, 2025.² In August 2024, the agent received a complete response letter in the aforementioned population due to an issue that arose during the inspection of a third-party fill/finish manufacturing facility.³

Supporting data from the pivotal, open-label, phase 1/2 LINKER-MM1 trial (NCT03761108) evaluating the safety and efficacy of linvoseltamab in patients with relapsed/refractory multiple myeloma were published in the Journal of Clinical Oncology.⁴

“Previous results from LINKER-MM1 have demonstrated that linvoseltamab has compelling efficacy characterized by deep and durable responses. With 14-months of median follow-up, 50% of patients achieved a complete response or better, despite their cancer being refractory to or relapsing on standard therapies,” Suzanne Lentzsch, MD, PhD, director of the Multiple Myeloma and Amyloidosis Program at Columbia University, stated in a press release.⁵ “Additionally, a study using US-based electronic health record data to indirectly compare linvoseltamab with real-world standard-of-care treatment also supports the overall body of evidence for this investigational medicine in heavily pretreated multiple myeloma.”

At the median follow-up of 14.3 months (range, 0.2-38.4), among patients who received 200 mg (n = 117), the overall response rate (ORR) was 70.9% and 49.6% achieved a complete response (CR) or better.³ Among those who received 50 mg (n = 104), at a median follow-up of 7.4 months (range, 0.4-42.0), the ORR was 48.1% and 21.2% achieved a CR or better.

In the 200 mg group, the median time to a partial response or greater was 1 month (range, 0.5-6.3), to a very good partial response (VGPR) or greater was 2.6 months (range, 0.7-15.7), and to a complete response or greater was 8.5 months (range, 1.6-14.1). Kaplan-Meier estimated median duration of response (DOR) was 29.4 months (95% CI, 16.2-not evaluable [NE]); the probability of maintaining a response at 12 months was 80.9% (95% CI, 70.3%-88.0%).

Kaplan-Meier estimated median progression-free survival (PFS) was not reached (95% CI, 17.3-NE) with a probability of being progression free at 12 months of 70.0% (95% CI, 60.1%-78.0%); median overall survival was 31.4 months (95% CI, 21.6-NE) with a probability of 12-month survival of 75.3% (95% CI, 66.0%-82.2%).

A total of 282 patients 18 years or older with relapsed/refractory multiple myeloma who had exposure to 3 or more prior lines of therapy were enrolled.

A full dose of intravenous linvoseltamab—either 50 mg or 200 mg—was administered once weekly from weeks 3 to 14, and then once every 2 weeks starting on week 16. Once a VGPR or better was achieved, patients at 200mg would switch to once every 4 weeks after a minimum of 24 weeks on treatment. Patients who received 50 mg were permitted dose escalation to 200 mg after weeks 4 to 14 of treatment.

Regarding safety, treatment-emergent adverse events (TEAEs) were similar between the 50 mg and 200 mg cohorts except for neutropenia, of which 41.9% of those in the 200 mg group experienced grade 3/4 vs 26.9% of the 50 mg group. TEAEs led to discontinuation in 18.8% of those receiving 200 mg and the majority were due to infections (9.4%), and death within 30 days of final treatment dose in 5.1% of patients given 200 mg.

The most common TEAEs of any grade in the 50 mg group, with a median treatment exposure of 13.9 months (range, 2.0-160.0), were cytokine release syndrome (54.8%), anemia (42.3%), cough (34.6%), and arthralgia (32.7%). Of the 200 mg group, with a median treatment exposure of 53.0 months (range, 1.0-167.0), the most common TEAEs were cytokine release syndrome (46.2%), neutropenia (42.7%), anemia (38.5%), and diarrhea (37.6%).

References

1. Linvoseltamab recommended for EU approval by the CHMP to treat relapsed/refractory multiple myeloma. News release. Regeneron. February 28, 2025. Accessed February 28, 2025. https://tinyurl.com/25zb63cs
2. Regeneron provides update on biologics license application for linvoseltamab. News release. Regeneron Pharmaceuticals, Inc. August 20, 2024. Accessed February 28, 2024. https://tinyurl.com/2u2pvw82
3. Linvoseltamab BLA accepted for FDA review for the treatment of relapsed/refractory multiple myeloma. News release. Regeneron Pharmaceuticals. February 11, 2025. Accessed February 28, 2025. https://tinyurl.com/y7hjbdub
4. Bumma N, Richter J, Jagannath S, et al. Linvoseltamab for treatment of relapsed/refractory multiple myeloma. J Clin Oncol. 2024;42(22):2702-2712. doi:10.1200/JCO.24.01008
5. Updated linvoseltamab data showcase continued deepening of responses in patients with heavily pre-treated multiple myeloma. News release. Regeneron. June 16, 2025. Accessed February 28, 2025. https://tinyurl.com/b5hx6m8m