Teclistamab-based induction treatment in transplant-eligible, newly diagnosed multiple myeloma: a phase 2 trial.

Publication date: Jun 25, 2026

Advancements in frontline therapies have substantially improved outcomes in newly diagnosed multiple myeloma (NDMM); however, many patients will not achieve deep responses and will relapse. Teclistamab, a BCMAcD7CD3 bispecific antibody, in combination with daratumumab, has demonstrated strong efficacy in relapsed/refractory multiple myeloma versus standard of care as early as first relapse. This ongoing phase 2 GMMG-HD10/DSMM-XX (MajesTEC-5) study evaluates teclistamab-based regimens in transplant-eligible NDMM. In this prespecified pooled analysis of three cohorts, 49 patients received teclistamab/daratumumab/lenalidomide (Tec-DR; arms A and A1) or Tec-DR with bortezomib (Tec-DVR; arm B). Primary endpoints were incidence and severity of adverse events (AEs) and serious AEs; secondary endpoints included overall response rate (ORR), minimal residual disease (MRD) negativity and MRD-negative complete response (CR). The current analysis spans the induction and autologous stem cell transplantation phases until the premaintenance timepoint. Grade 3 or 4 treatment-emergent AEs (TEAEs) occurred in 91. 8% (45/49); most were hematologic (lymphopenia (59. 2%; 29/49), neutropenia (59. 2%; 29/49) and leukopenia (18. 4%; 9/49)). No grade 5 TEAEs were reported. Serious AEs occurred in 55. 1% (27/49); pyrexia (12. 2% (6/49)) was most common. Any-grade and grade 3 or 4 infections occurred in 81. 6% (40/49) and 36. 7% (18/49), respectively, the most common grade 3 or 4 infections being COVID-19 and pneumonia (6. 1% (3/49) each). Cytokine release syndrome occurred in 67. 3% (33/49); all were grade 1 or 2, all resolved and none led to discontinuation of any study treatment. No treatment-related immune effector cell-associated neurotoxicity syndrome (ICANS) events occurred. Across arms, the MRD-negative CR rate was 91. 8% (45/49) by the premaintenance timepoint; the MRD negativity rate was 100% in evaluable samples at postinduction cycle 3 (1 cD7 10 (46/46)), cycle 6 (1 cD7 10 (46/46) and 1 cD7 10 (46/46)) and premaintenance (1 cD7 10 (40/40)); the ORR was 100% (49/49). Total median stem cell yield was 8. 1 cD7 10 per kg. Data support the feasibility of Tec-D(V)R induction in transplant-eligible NDMM, with a consistent safety profile compared with individual regimen components and notable early MRD negativity rates. ClinicalTrials. gov identifier: NCT05695508 .

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