MajesTEC-5: A phase II trial of teclistamab-based induction for transplant-eligible NDMM

Results from a prespecified pooled analysis of three induction cohorts from the ongoing phase II MajesTEC-5 (NCT05695508) trial, evaluating teclistamab-based induction in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM), were published in Nature Medicine by Raab et al. The analysis included 49 patients who received teclistamab + daratumumab + lenalidomide (Tec-DR; Arms A/A1, n = 30) or Tec-DR + bortezomib (Tec-DVR; Arm B, n = 19), with outcomes assessed from induction, through autologous hematopoietic stem cell transplantation (auto-HSCT), and to last visit prior to initiation of maintenance therapy. The primary endpoints were the incidence and severity of adverse events (AEs) and serious AEs.

Key data: At a median follow-up of 12.3 months, all patients experienced a treatment-emergent adverse event (TEAE). Grade 3/4 TEAEs occurred in 91.8% and were predominantly hematologic, including lymphopenia (59.2%), neutropenia (59.2%), and leukopenia (18.4%). Grade 3/4 infections occurred in 36.7% of patients, while cytokine release syndrome (CRS) occurred in 67.3% (all Grade 1/2 and resolved). Serious TEAEs occurred in 55.1% of patients, and no treatment-related immune effector cell-associated neurotoxicity syndrome (ICANS) was reported. At premaintenance, the cumulative measurable residual disease (MRD)-negative complete response (CR) rate was 91.8% and the overall response rate (ORR) was 100%. 

Key learning: Teclistamab-based induction with daratumumab and lenalidomide, with or without bortezomib, was feasible before auto-HSCT, with a consistent safety profile compared with the individual components and early MRD negativity rates, supporting continued evaluation as an immune-based, steroid-sparing first-line strategy for transplant-eligible NDMM.