Posted: Thursday, June 15, 2023
More may be better, it seems, when it comes to linvoseltamab (formerly REGN5458), a B-cell maturation antigen (BCMA) × CD3 bispecific antibody being studied in patients with heavily pretreated relapsed or refractory multiple myeloma. Linvoseltamab at 200 mg had higher efficacy compared with 50 mg, including in patients with high disease burden, in phase II of the LINKER-MM1 study, designed to optimize dose selection. Thus, the recommended linvoseltamab dose for further development is 200 mg, reported Hans C. Lee, MD, of The University of Texas MD Anderson Cancer Center, Houston, and colleagues at the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 8006).
The 179 patients in the phase II portion of LINKER-MM1 had a median age of 66 years; 81% were triple-class–refractory or higher. Their overall response rate—the primary endpoint—was 64% with 200 mg (n = 75) versus 50% with 50 mg (n = 104), and the probability of maintaining response at 6 months was 89% (200 mg) and 85% (50 mg). Further, the research team reported, subgroup analyses showed a higher overall response rate in the 200-mg cohort versus the 50-mg cohort for patients with a soluble BCMA concentration of at least 0.4 mg/L (52% vs. 37%, respectively), those with bone marrow plasma cell percentage higher than 67% (64% vs. 35%), and those with revised International Staging System stage III disease (71% vs. 27%).
Safety was reported to be consistent across both doses. Treatment-emergent adverse events leading to treatment discontinuation occurred in 7% and 8% of the 200-mg and 50-mg cohorts, respectively. However, the occurrence of treatment-emergent adverse events was high, affecting 95% (grade ≥ 3, 66%) of patients in the 200-mg cohort and 100% (grade ≥ 3, 80%) of those in the 50-mg cohort. The most common of these events were cytokine-release syndrome, fatigue, and anemia, noted Dr. Lee and co-investigators.
Disclosure: The study authors’ disclosure information can be found at coi.asco.org.