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

Abstract 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 BCMA×CD3 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 × 10 −5 (46/46)), cycle 6 (1 × 10 −5 (46/46) and 1 × 10 −6 (46/46)) and premaintenance (1 × 10 −5 (40/40)); the ORR was 100% (49/49). Total median stem cell yield was 8.1 × 10 6 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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Journal
Nature Medicine
Published
2026-06-25
DOI
https://doi.org/10.1038/s41591-026-04471-x
Primary Topic
Multiple Myeloma Research and Treatments
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article
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0.00

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article

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

Natalie Schub, Hermann Einsele, Katja Christina Weisel, Leo Rasche et al.
Nature Medicine
Multiple Myeloma Research and Treatments
article

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

Natalie Schub, Hermann Einsele, Katja Christina Weisel, Leo Rasche, Stefanie Huhn, Jan Krönke, Carsten Müller‐Tidow, Alexander Brobeil, Bas D. Koster, Niels Weinhold, Josephine Khan, Hartmut Goldschmidt, Raphael Teipel, Florian C. Bassermann, K. Martin Kortüm, Hans Salwender, Marc S. Raab, Michael Hundemer, Ryan Arlinghaus, Johannes M. Waldschmidt, Julia Mersi, K. Elias, Lilli Podola, Elena Ershova, K. Martin Kortüm, R Fenk, Christoph Heuck, Mathias Hänel, Monika Engelhardt, Caline Sakabedoyan, Stephan R. Bohl, on behalf of the GMMG-HD10/DSMM-XX (MajesTEC-5) investigators, Uta Bertsch
article en

Abstract

Abstract 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 BCMA×CD3 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 × 10 −5 (46/46)), cycle 6 (1 × 10 −5 (46/46) and 1 × 10 −6 (46/46)) and premaintenance (1 × 10 −5 (40/40)); the ORR was 100% (49/49). Total median stem cell yield was 8.1 × 10 6 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 .

Nature Medicine
Johnson & Johnson (United States) (US), Universität Hamburg (DE), University of Freiburg (DE), Heidelberg University (DE), University Medical Center Freiburg (DE), University Hospital Heidelberg (DE), TUM Klinikum (DE), LMU Klinikum (DE), Humboldt-Universität zu Berlin (DE), Asklepios Klinik Altona (DE), Düsseldorf University Hospital (DE), Johnson & Johnson (France) (FR), University Medical Center Hamburg-Eppendorf (DE), University Hospital Schleswig-Holstein (DE), München Klinik (DE), German Marine Research Consortium (DE), Asklepios Klinik St. Georg (DE), Universitätsklinikum Würzburg (DE), Johnson & Johnson (United Kingdom) (GB), DKFZ-ZMBH Alliance (DE), Johnson & Johnson (Netherlands) (NL), Klinikum Chemnitz (DE), Klinik und Poliklinik für Psychotherapie und Psychosomatik (DE), Heinrich Heine University Düsseldorf (DE), Freie Universität Berlin (DE), Charité - Universitätsmedizin Berlin (DE), University of Lübeck (DE)
Amgen, Bristol-Myers Squibb, Pfizer, AstraZeneca, GlaxoSmithKline, Sanofi, Celgene, Jazz Pharmaceuticals, Universitätsklinikum Heidelberg, Johnson and Johnson
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Openalex Percentile: Top 8%
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