Shaji Kumar, Sundar Jagannath, Katja C. Weisel, Laura Rosiñol, Xavier Leleu, Meletios-Athanasios Dimopoulos, Efstathios Kastritis, David S. Siegel, Jorge Monge, Juan Du, Javier de la Rubia, Pedro Asensi Cantó, Jae Kyoung Lee, María-Victoria Mateos, Borja Puertas, Alessandro Gozzetti, Dominik Dytfeld, Enrique M. Ocio, Joan Blade, Shuji Ozaki, Meral Beksac, F Escalante, Madhu Nagaraj, Rafla Hassan, Nicolle Bonar, Paul Spin, Mostafa Shokoohi, Muhaimen Siddiqui, Di Wang, Kevin Hou, Michael E. West, Christian Hampp, Jeannette Green, Olivier Humblet, Alexander Breskin, James Harnett, Wenzhen Ge, Rachel E. Sobel, Jessica J. Jalbert, Glenn S. Kroog, Karen Rodriguez Lorenc, Qiufei Ma, B G M Durie
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.