Journal Article Ahead of print
PubMed: 41881954 DOI: 10.1038/s41408-026-01466-2
Linvoseltamab versus real-world International Myeloma Working Group standard-of-care in triple-class exposed relapsed/refractory multiple myeloma.
Blood Cancer J
Authors: 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 Hoon Lee, María-Victoria Mateos, Borja Puertas, Alessandro Gozzetti, Dominik Dytfeld, Enrique M Ocio, Joan Blade, Shuji Ozaki, Meral Beksac, Fernando Escalante, Madhu Nagaraj, Rafla Hassan, Nicolle Bonar, Paul Spin, Mostafa Shokoohi, Muhaimen Siddiqui, Di Wang, Kevin Hou, Michael E D 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, Brian G M Durie
Affiliations
- Mayo Clinic, Rochester, MN, USA.
- Mount Sinai Hospital, New York, NY, USA.
- University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain.
- Centre Hospitalier Universitaire, Poitiers, France.
- School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
- Korea University, Seoul, South Korea.
- Hackensack University Medical Center, Hackensack, NJ, USA.
- University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
- Shanghai Changzheng Hospital, Shanghai, China.
- Hospital La Fe, Valencia, Spain.
- Gachon University Gil Medical Center, Incheon, South Korea.
- University Hospital of Salamanca, IBSAL/Cancer Research Center-IBMCC (USAL-CSIC), CIBERONC, Salamanca, Spain.
- University of Siena, Siena, Italy.
- Karol Marcinkowski University of Medical Sciences, Poznań, Poland.
- Hospital Universitario Marqués de Valdecilla, Santander, Spain.
- Tokushima Prefectural Central Hospital, Tokushima, Japan.
- Istinye University, Ankara, Turkey.
- Complejo Asistencial Universitario de León, IBIOLEON, León, Spain.
- Mayo Clinic, Rochester, MN, USA.
- EVERSANA, Burlington, ON, Canada.
- Regeneron Pharmaceuticals Inc. Tarrytown, NY, USA.
- Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Abstract
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.
MeSH
Multiple Myeloma, Therapeutics