Dr Richter on the Optimal Dosing Schedule of Linvoseltamab in Multiple Myeloma

Joshua Richter, MD, associate professor of medicine, Tisch Cancer Institute, Division of Hematology and Medical Oncology, director of Multiple Myeloma, Blavatnik Family Chelsea Medical Center, Mount Sinai, discusses findings from the phase 1/2 LINKER-MM1 trial (NCT03761108) in multiple myeloma.

Linvoseltamab is a BCMA- and CD3-directed bispecific antibody that is under evaluation in patients with relapsed/refractory multiple myeloma. In this study, 50 mg and 200 mg of linvoseltamab were evaluated, the latter of which is more patient friendly in terms of administration schedule, Richter says. In the 50-mg cohort, patients received step-up doses of 5 mg and 25 mg in weeks 1 and 2 before ramping up to 50 mg weekly for 3 cycles. From cycle 4 on, linvoseltamab was administered at 50 mg every 2 weeks. In the 200-mg cohort, patients received 5 mg on day 1 and 25 mg on day 8, 200 mg every week for 3 cycles, and 200 mg every 2 weeks thereafter. If very good partial response was achieved, patients could continue reduce the frequency between doses to every 4 weeks.

To be eligible for enrollment, patients had to have progressed on or after at least 3 prior lines of therapy, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. The primary end point was objective response rate (ORR) per blinded independent review committee assessment. Secondary end points included progression-free survival (PFS) and overall survival.

As of February 28, 2023, 104 patients had been treated in the 50-mg cohort and 117 patients had been treated in the 200-mg cohort. With median durations of follow-up of 7.7 months (range, 0.3-31.3) and 5.6 months (range, 0.2-28.2) in the 50- and 200-mg cohorts, respectively, the ORRs were 50% and 71%, respectively. The recommended dose was established at 200 mg, in which 16% of patients experienced stringent complete response (CR), 14% experienced CR, 29% experienced very good partial response, and 12% experienced partial response. Median PFS was not reached with the 200-mg dose, with 3- and 6-month PFS rates of 79.6% and 72.7%, respectively. Moreover, median time to response was 0.95 months (range, 0.76-1.84).

Regarding safety, cytokine release syndrome (CRS) occurred in 45.3% of patients, only 1 of which experienced a grade 3 event. Any-grade immune effector cell–associated neurotoxicity occurred in 5.9% of patients, with grade 3/4 events occurring in 1.8%. None of the six deaths reported in the 200-mg arm were considered treatment related. Infections represented the most common grade 3 or greater toxicity, at 36.8%. Safety data from this trial indicate that the traditional understanding that higher doses of treatment, historically with chemotherapy, lead to increased toxicity is not applicable to the realm of immunotherapy, Richter concludes.