Teclistamab-based induction treatment in transplant-eligible, newly diagnosed multiple myeloma: a phase 2 trial
23 affiliations
- 1Heidelberg Myeloma Center and GMMG Study Group, Department of Medicine V, Heidelberg University Hospital and Medical Faculty Heidelberg, Heidelberg, Germany. [email protected]
- 2Heidelberg Myeloma Center and GMMG Study Group, Department of Medicine V, Heidelberg University Hospital and Medical Faculty Heidelberg, Heidelberg, Germany
- 3Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany
- 4Department of Hematology, Oncology, and Tumor Immunology, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
- 5Deutsches Konsortium für Translationale Krebsforschung (DKTK), Partner Site Berlin, Berlin, Germany
- 6Department of Hematology, Oncology and Clinical Immunology, University Hospital Düsseldorf, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
- 7University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- 8Institute of Pathology, University Hospital Heidelberg, Heidelberg, Germany
- 9Coordination Centre for Clinical Trials (KKS), University Hospital Heidelberg, Heidelberg, Germany
- 10Department of Internal Medicine II, Division of Stem Cell Transplantation and Immunotherapy, Universitätsklinikum Schleswig-Holstein (UKSH) Campus Kiel, Kiel, Germany
- 11Bayerisches Zentrum für Krebsforschung (BZKF), Munich, Germany
- 12Department of Medicine III, TUM Klinikum, Technische Universität München, München, Germany
- 13Deutsches Konsortium für Translationale Krebsforschung (DKTK), Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany
- 14Johnson & Johnson, Spring House, PA, USA
- 15Johnson & Johnson, Paris, France
- 16Johnson & Johnson, High Wycombe, UK
- 17Johnson & Johnson, Beerse, Belgium
- 18Johnson & Johnson, Leiden, The Netherlands
- 19Department of Hematology, Oncology and Stem Cell Transplantation, Medical Centre - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany
- 20Department of Internal Medicine III, Klinikum Chemnitz, Chemnitz, Germany
- 21Asklepios Tumorzentrum Hamburg, Asklepios Klinik Altona and Asklepios Klinik St. Georg, Hamburg, Germany
- 22Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus an der Technische Universität Dresden, Dresden, Germany
- 23Department of Internal Medicine II, University Hospital of Würzburg, Würzburg, Germany. [email protected]
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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BibTeX
@article{raab2026teclistamabbased,
title = {{Teclistamab-based induction treatment in transplant-eligible, newly diagnosed multiple myeloma: a phase 2 trial}},
author = {Marc Steffen Raab and Niels Weinhold and Klaus Martin Kortüm and Jan Krönke and Roland R. Fenk and Katja Christina Weisel and Lilli Podola and Uta Bertsch and Alexander Brobeil and Julia Mersi and Stefanie Huhn and Ryan Arlinghaus and Michael Hundemer and Stephan Bohl and Elias Karl Mai and Natalie Schub and Johannes Moritz Waldschmidt and Florian C. Bassermann and Carsten Müller‐Tidow and Christoph Johann Heuck and Caline Sakabedoyan and Josephine Khan and Elena Ershova and Bas D. Koster and Monika Martha Engelhardt and Mathias Hänel and Hans Jürgen Salwender and Raphael Teipel and Hartmut Goldschmidt and Hermann Einsele and Leo Rasche and on behalf of the GMMG-HD10/DSMM-XX (MajesTEC-5) investigators and K. Martin Kortüm},
journal = {Nature Medicine},
year = {2026},
month = jun,
doi = {10.1038/s41591-026-04471-x},
url = {https://doi.org/10.1038/s41591-026-04471-x},
note = {CC BY},
}
RIS
TY - JOUR
TI - Teclistamab-based induction treatment in transplant-eligible, newly diagnosed multiple myeloma: a phase 2 trial
AU - Marc Steffen Raab
AU - Niels Weinhold
AU - Klaus Martin Kortüm
AU - Jan Krönke
AU - Roland R. Fenk
AU - Katja Christina Weisel
AU - Lilli Podola
AU - Uta Bertsch
AU - Alexander Brobeil
AU - Julia Mersi
AU - Stefanie Huhn
AU - Ryan Arlinghaus
AU - Michael Hundemer
AU - Stephan Bohl
AU - Elias Karl Mai
AU - Natalie Schub
AU - Johannes Moritz Waldschmidt
AU - Florian C. Bassermann
AU - Carsten Müller‐Tidow
AU - Christoph Johann Heuck
AU - Caline Sakabedoyan
AU - Josephine Khan
AU - Elena Ershova
AU - Bas D. Koster
AU - Monika Martha Engelhardt
AU - Mathias Hänel
AU - Hans Jürgen Salwender
AU - Raphael Teipel
AU - Hartmut Goldschmidt
AU - Hermann Einsele
AU - Leo Rasche
AU - on behalf of the GMMG-HD10/DSMM-XX (MajesTEC-5) investigators
AU - K. Martin Kortüm
PY - 2026
DA - 2026/06/25
JO - Nature Medicine
DO - 10.1038/s41591-026-04471-x
UR - https://doi.org/10.1038/s41591-026-04471-x
AB - 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 .
SN - 1078-8956
SN - 1546-170X
SN - 1744-7933
ER -