Linvoseltamab for Treatment of Relapsed/Refractory Multiple Myeloma
Naresh Bumma, Joshua Richter, Sundar Jagannath, Hans C. Lee, James E. Hoffman, Attaya Suvannasankha, Jeffrey A. Zonder, Mansi Shah, Suzanne Lentzsch, Rachid Baz, Joseph Maly, Swathi Namburi, Matthew J. Pianko, Jing Christine Ye, Ka Lung Wu, Rebecca Silbermann, Chang‐Ki Min, Marie‐Christiane Vekemans, Markus Munder, Ja Min Byun, Joaquín Martínez‐López, Kaniel Cassady, Michelle DeVeaux, Dhruti Chokshi, Anita Boyapati, Anasuya Hazra, George D. Yancopoulos, L. Andres Sirulnik, Karen Rodriguez Lorenc, Glenn S. Kroog, Yariv Houvras, Madhav V. Dhodapkar
Abstract
PURPOSE: We present a phase I/II first-in-human trial evaluating the safety and efficacy of 50 mg and 200 mg doses of linvoseltamab, a B-cell maturation antigen × CD3 bispecific antibody in relapsed/refractory multiple myeloma (RRMM). METHODS: Phase II eligible patients had RRMM that either progressed on/after ≥three lines of therapy including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 antibody or was triple-class (PI/IMiD/anti-CD38) refractory. Phase II treatment was once a week through week 14 and then once every 2 weeks. Phase II 200 mg patients who achieved a ≥very good partial response by week 24 received linvoseltamab once every 4 weeks. The primary end point in phase II was overall response rate (ORR). RESULTS: Among the 117 patients treated with 200 mg, the median age was 70 years, 39% had high-risk cytogenetics, and 28% had penta-refractory disease. At a median follow-up of 14.3 months, the ORR was 71%, with 50% achieving ≥complete response (CR). In 104 patients treated with 50 mg at a median follow-up of 7.4 months, the ORR was 48%, with 21% achieving ≥CR. The median duration of response (DOR) for 200 mg patients (n = 83) was 29.4 months (95% CI, 19.2 to not evaluable). Among 200 mg patients, the most common adverse events included cytokine release syndrome (35.0% Gr1, 10.3% Gr2, 0.9% Gr3), neutropenia (0.9% Gr2, 18.8% Gr3, 23.1% Gr4), and anemia (3.4% Gr1, 4.3% Gr2, 30.8% Gr3). Immune effector cell-associated neurotoxicity syndrome occurred in 7.7% of patients (2.6% each Gr1, Gr2, Gr3). Infections were reported in 74.4% of patients (33.3% Gr3, 2.6% Gr4); infection frequency and severity declined over time. CONCLUSION: Linvoseltamab 200 mg induced deep and durable responses, with a median DOR of 29.4 months, in patients with RRMM with an acceptable safety profile.