Dr Lee on the Significance of Longer-Term 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 how longer-term efficacy and safety data with linvoseltamab (REGN5458) derived from the phase 2 LINKER-MM1 study (NCT03761108) may potentially impact treatment approaches in relapsed/refractory multiple myeloma.

The study investigated linvoseltamab, a BCMA/CD3-directed bispecific antibody, in a heavily pretreated patient population with relapsed/refractory multiple myeloma which demonstrated promising results in terms of efficacy and safety. The dose escalation/expansion study enrolled patients who had progressed on multiple lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody, or who were triple-class refractory.

Patients enrolled onto the dose-expansion portion of the study underwent step-up dosing with linvoseltamab, followed by a 24-hour hospitalization period, Lee details. The weekly step-up dosing regimen, starting with 5 mg on day 1 and 25 mg on day 8, differentiated linvoseltamab from other treatments. During the initial 3 treatment cycles, patients were administered 200 mg of linvoseltamab once weekly. Subsequently, in cycles 4 and 5, the dosage was modified to 200 mg every 2 weeks. Starting from cycle 6, patients achieving a very good partial response (VGPR) or higher received the agent at a dosage of 200 mg every 4 weeks. Those who did not achieve a VGPR continued to receive the agent at a dosage of 200 mg every 2 weeks. This weekly step-up dosing regimen was a notable distinguishing feature of linvoseltamab, Lee notes.

Long-term data from the study presented at the 2023 ASH Annual Meeting, showed high response rates with linvoseltamab, with an overall response rate (ORR) of 69% at a median follow-up of 8.1 months, Lee reports. Furthermore, the median duration of response and progression-free survival (PFS) were not reached, with estimated 9-month rates of 86.8% and 72.8%, respectively. Importantly, linvoseltamab exhibited a generally manageable toxicity profile with no new safety signals identified.

Additional data from the LINKER-MM1 study, published later in 2023, demonstrated even higher ORR of 71% as adjudicated by an independent review committee and a complete response rate of 46% at an 11-month median follow-up, Lee reports. These findings suggest that linvoseltamab shows continued efficacy, durability of responses, and encouraging safety signals in relapsed/refractory multiple myeloma, Lee explains.

The rapid de-escalation of dosing frequency, limited hospitalization requirements for cytokine release syndrome (CRS) monitoring, and low CRS rates make linvoseltamab a promising approach for the treatment of patients with relapsed/refractory multiple myeloma, Lee concludes.