Indirect comparison of linvoseltamab versus teclistamab for triple-class exposed (TCE) relapsed/refractory multiple myeloma (RRMM).

person Sundar Jagannath Icahn School of Medicine at Mount Sinai, New York, NY info_outline Sundar Jagannath, Hans C. Lee, Joshua Ryan Richter, Jeffrey A. Zonder, James E. Hoffman, Zheng-Yi Zhou, Viviana Garcia Horton, Mirko Fillbrunn, Hongjue Wang, Matthew Mattera, Qiufei Ma, Timothy J Inocencio, Yingxin Xu, Evelien Bergrath, James Harnett, Tito Roccia, Glenn Scott Kroog, Karen Rodriguez-Lorenc, Yariv Houvras, Naresh Bumma

Authors person Sundar Jagannath Icahn School of Medicine at Mount Sinai, New York, NY info_outline Sundar Jagannath, Hans C. Lee, Joshua Ryan Richter, Jeffrey A. Zonder, James E. Hoffman, Zheng-Yi Zhou, Viviana Garcia Horton, Mirko Fillbrunn, Hongjue Wang, Matthew Mattera, Qiufei Ma, Timothy J Inocencio, Yingxin Xu, Evelien Bergrath, James Harnett, Tito Roccia, Glenn Scott Kroog, Karen Rodriguez-Lorenc, Yariv Houvras, Naresh Bumma Organizations Icahn School of Medicine at Mount Sinai, New York, NY, Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, Karmanos Cancer Institute, Detroit, MI, University of Miami Health System, Miami, FL, Analysis Group, Inc., Boston, MA, Regeneron Pharmaceuticals, Inc., Tarrytown, NY, The Ohio State University Comprehensive Cancer Center, Columbus, OH Abstract Disclosures Research Funding Regeneron Pharmaceuticals, Inc Background: No head-to-head clinical trials have compared effectiveness of anti-BCMA×CD3 bispecific antibodies for TCE RRMM. This analysis compared efficacy of linvoseltamab vs teclistamab via an unanchored matching-adjusted indirect comparison (MAIC). Methods: A MAIC was deemed feasible after excluding 10 patients (pts) with prior BCMA antibody–drug conjugate exposure from LINKER-MM1 (linvoseltamab) to match MajesTEC-1 (teclistamab) criteria. Pt-level data from LINKER-MM1 (107 pts receiving 200 mg in Phase 1/2, data cut-off [DCO] 9/2023, median follow-up 11.1 months [mos]) and published data from MajesTEC-1’s efficacy population (150 pts, DCO 11/2021, median follow-up 9.8 mos) were analyzed. LINKER-MM1 pts were weighted to match key baseline characteristics in MajesTEC-1 (cytogenetic risk, age, refractory status, ISS stage, ECOG score, extramedullary disease/plasmacytoma status) selected via a prespecified algorithm (Kumar et al., 2023). Objective response rate (ORR), very good partial response or better (≥VGPR), complete response or better (≥CR), and minimal residual disease (MRD) negativity (- [at 10-5 threshold]) rates, duration of response (DOR), progression-free survival (PFS), and overall survival (OS) were compared. Odds ratios (ORs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were reported before and after matching; a sensitivity analysis included all LINKER-MM1 200 mg pts (n=117). Results: Effective sample size for linvoseltamab was 82 after matching and baseline characteristics were balanced with MajesTEC-1. Before and after matching, linvoseltamab exhibited higher ORR, ≥VGPR, ≥CR, and MRD(-) rates, with significant differences in ≥CR. Linvoseltamab had significantly longer PFS and a trend toward longer OS and DOR (Table). Sensitivity analysis results were similar. Conclusions: The results suggest potentially greater efficacy for linvoseltamab vs teclistamab for all outcomes, highlighting its potential as a highly effective treatment option for TCE RRMM. Teclistamab Linvoseltamab before matching Linvoseltamab after matching Linvoseltamab vs teclistamab before matching Linvoseltamab vs teclistamab after matching % % % OR (CI) OR (CI) ORR 63 71 70 1.46 (0.98, 2.18) 1.42 (0.91, 2.22) ≥VGPR 59 63 61 1.18 (0.82, 1.70) 1.10 (0.74, 1.65) ≥CR 32 47 45 1.86 (1.28, 2.71)* 1.75 (1.17, 2.62)* MRD(-) 13 20 19 1.59 (0.90, 2.82) 1.55 (0.84, 2.84) Median, mos (CI) Median, mos (CI) Median, mos (CI) HR (CI) HR (CI) DOR Not reached (NR) (not estimable [NE], NE) NR (NE, NE) NR (NE, NE) 0.94 (0.46, 1.90) 0.82 (0.38, 1.73) PFS 10.10 (8.00, NE) NR (14.72, NE) NR (15.47, NE) 0.56 (0.37, 0.86)* 0.53 (0.33, 0.86)* OS 18.27 (18.27, NE) NR (21.62, NE) NR (21.62, NE) 0.75 (0.46, 1.22) 0.77 (0.45, 1.31) *Statistically significant at p<0.05 OR >1 or HR <1 indicate better efficacy for linvoseltamab.