Dr Lee on the Updated Efficacy and Safety Data for Linvoseltamab in R/R Multiple Myeloma

Hans C. Lee, MD, associate professor, Department of Lymphoma/Myeloma, Multiple Myeloma Clinical Research, Department of Lymphoma/Myeloma, Division of Cancer Medicine, the University of Texas MD Anderson Cancer Center, discusses updated data from the phase 2 LINKER-MM1 study (NCT03761108) investigating the BCMA/CD3-directed bispecific antibody linvoseltamab (REGN5458) in patients with relapsed/refractory multiple myeloma.

The first-in-human, dose escalation/expansion study enrolled heavily pretreated patients who had either progressed on or after 3 or more lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody, or patients who were triple-class refractory. In the dose-expansion portion of the investigation, participants underwent step-up dosing with linvoseltamab, receiving 5 mg on day 1 and 25 mg on day 8, followed by a 24-hour hospitalization period. For the first 3 treatment cycles, patients received 200 mg of linvoseltamab once a week. In cycles 4 and 5, the dosage was adjusted to 200 mg every 2 weeks. From cycle 6 onward, individuals achieving a very good partial response (VGPR) or higher received the agent at 200 mg every 4 weeks. Patients whose disease did not attain a VGPR continued to receive the agent at 200 mg every 2 weeks.

Long-term data from the study were presented at the 2023 ASH Annual Meeting. At a median follow-up of 8.1 months, responses with linvoseltamab remained effective and had deepened since the prior analysis at a median follow-up of 5.6 months, Lee reports. At the recommended dose of 200 mg, the agent produced an overall response rate (ORR) of 69%, Lee adds, 59% of which were VGPRs or higher and 39% of which were complete responses (CRs). Of those who achieved a CR or sCR with available minimal residual disease data, 59% did not show measurable residual disease.

Additionally, the median time to response with linvoseltamab was 1 month. The median duration of response and PFS was not reached, although estimated 9-month rates were 86.8% and 72.8%, respectively.

Regarding safety, linvoseltamab had a generally manageable toxicity profile with no new safety signals at the time of follow-up, Lee states. Overall, these data show that linvoseltamab produces early, durable, and high responses in pretreated patients with relapsed/refractory multiple myeloma, supporting the agent's ongoing investigation in the phase 3 LINKER-MM3 trial (NCT05730036).