Linvoseltamab versus real-world International Myeloma Working Group standard-of-care in triple-class exposed relapsed/refractory multiple myeloma

LINKER-MM1 (NCT03761108) is a Phase 1/2 study of linvoseltamab, a human BCMA×CD3 bispecific antibody for patients with relapsed/refractory multiple myeloma (RRMM) who are triple-class exposed (TCE) with ≥ 3 prior lines of therapy (3L+), or triple-class refractory (TCR). To contextualize efficacy data from LINKER-MM1, the Phase 2 linvoseltamab 200 mg cohort (N = 105) was compared with an international external control arm (ECA) comprising 203 patients from participating International Myeloma Working Group sites who met LINKER-MM1 eligibility criteria based on chart reviews. The ECA reflected real-world standard-of-care (RW SOC). An independent data review committee assessed data relevance, quality, and cohort comparability, while a separate independent central review committee evaluated response data. Inverse probability of treatment weighting was used to balance baseline characteristics between the linvoseltamab arm and the ECA. Linvoseltamab had a higher objective response rate (weighted odds ratio 3.0 95% confidence interval (CI): 1.9-4.1) and longer median progression-free survival (weighted hazard ratio wHR 0.33 95% CI: 0.28-0.40), time to next treatment (wHR 0.34 95% CI: 0.29-0.44), and overall survival (wHR 0.72 95% CI: 0.58-0.98) than RW SOC. These findings highlight linvoseltamab's potential as an effective treatment for 3L+ and TCE/TCR RRMM.