Shaji Kumar, Katja C. Weisel, Paul Spin, Nicolle Bonar, Muhaimen Siddiqui, Mostafa Shokoohi, Di Wang, Kevin Hou, Michael E. West, Christian Hampp, Jeannette Green, James Harnett, Olivier Humblet, Alexander Breskin, Wenzhen Ge, Jessica J. Jalbert, Rachel E. Sobel, G. Kroog, Karen Rodriguez Lorenc, Qiufei Ma, Sundar Jagannath
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). The Phase 2 linvoseltamab 200 mg cohort (N = 105) was compared with an external control arm comprising 149 patients from two US electronic health record databases, COTA and Guardian Research Network, treated with real-world (RW) standard-of-care (SOC). Key LINKER-MM1 eligibility criteria were applied to the RW SOC cohort; an independent data review committee assessed data relevance and quality, and cohort comparability. Inverse probability of treatment weighting was used to balance baseline characteristics between cohorts. The most common SOC regimens were combinations of carfilzomib, pomalidomide, and dexamethasone (8.6%) and daratumumab, pomalidomide, and dexamethasone (8.2%). No patients received chimeric antigen receptor T cell therapy or bispecific antibodies. Linvoseltamab had a higher objective response rate than RW SOC (weighted odds ratio 3.8 [95% CI: 2.5-6.6]), and longer median progression-free survival (weighted hazard ratio [wHR] 0.29 [95% CI: 0.23-0.39]), time to next treatment (wHR 0.20 [95% CI: 0.15-0.26]), and overall survival (wHR 0.41 [95% CI: 0.32-0.52]), demonstrating its potential as an effective treatment for 3L+ and TCE/TCR RRMM.