Indirect Comparison of Linvoseltamab Versus Teclistamab for the Treatment of Triple-Class Exposed Relapsed/Refractory Multiple Myeloma

Clin Lymphoma Myeloma Leuk. 2025 Dec;25(12):897-909.e8. doi: 10.1016/j.clml.2025.06.014. Epub 2025 Jun 22.

Abstract

Background: B-cell maturation antigen (BCMA) bispecific antibodies have advanced treatment of relapsed/refractory multiple myeloma (RRMM), but comparative data are lacking.

Methods: An unanchored matching-adjusted indirect comparison (MAIC) was conducted between linvoseltamab and teclistamab in triple-class exposed (TCE) RRMM using patient-level data from LINKER-MM1 (117 patients, linvoseltamab 200 mg, data cutoff 1/2024, median follow-up [mFU] 14.3 months) and aggregate data from MajesTEC-1 (165 patients, teclistamab 1.5 mg/kg, data cutoff 2/2022, mFU 14.1 months). Ten LINKER-MM1 patients with prior BCMA antibody-drug conjugate exposure were excluded to match MajesTEC-1 eligibility criteria. LINKER-MM1 patients were weighted to match MajesTEC-1 on 6 prespecified prognostic factors considered most important by an international MM expert panel.

Results: After matching (effective sample size = 83.0), linvoseltamab showed significantly longer progression-free survival (PFS, P = .004), overall survival (OS, P = .039), and time to next treatment (P = .028), and numerically longer duration of response ((P = .100) than teclistamab based on hazard ratios. Linvoseltamab demonstrated numerically higher objective response rate, very good partial response or better, complete response or better (≥CR), and minimal residual disease-negativity (10-5 threshold) rates versus teclistamab based on odds ratios. Additional MAICs matching all prognostic factors available in both trials showed significantly longer PFS (P = .038) and OS (P = .039), significantly higher ≥CR (P = .043), and favorable trends for all other outcomes.

Conclusion: This analysis demonstrated statistically improved PFS and OS and numerically favorable results for all other outcomes for linvoseltamab versus teclistamab in the treatment of TCE RRMM.

Keywords: Bispecific antibodies; Clinical efficacy; Linvoseltamab; Relapsed/refractory multiple myeloma; Teclistamab.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Bispecific* / pharmacology
  • Antibodies, Bispecific* / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma* / drug therapy
  • Multiple Myeloma* / mortality
  • Multiple Myeloma* / pathology
  • Neoplasm Recurrence, Local* / drug therapy

Substances

  • Antibodies, Bispecific