TECLISTAMAB PLUS DARATUMUMAB (TEC-DARA) IN PATIENTS (PTS) WITH RELAPSED REFRACTORY MULTIPLE MYELOMA (RRMM): ANALYSIS OF MAJESTEC-3 BASED ON CYTOGENETIC AND FUNCTIONAL RISK
40 affiliations
- 1Fred Hutchinson Cancer Center, Seattle, United States
- 2Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Netherlands
- 3Winship Cancer Institute, Emory University, Atlanta, Georgia, States
- 4Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Instituto de Biología Molecular y Celular del Cáncer Salamanca, Spain
- 5Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, Canada
- 6Universite de Toulouse, Centre Hospitalier Universitaire, Service d’Hematologie, IUCT Oncopole CRCT, Toulouse, France
- 7Emory University, Winship Cancer Institute, Atlanta, GA, United States
- 8Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China
- 9The Royal Marsden NHS Foundation Trust, London, United Kingdom
- 10Hospital Privado Centro Medico de Córdoba SA, Córdoba, Argentina
- 11Department of Hematology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium
- 12Clínica São Germano, São Paulo, SP, Brazil
- 13Department of Hematology, Rigshospitalet, Copenhagen, Denmark
- 1416Department of Hematology, Odense University Hospital, Odense, Denmark
- 15Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany
- 16Department of Internal Medicine II, University Tübingen, Tübinge, Germany
- 17Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
- 18IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia “Seràgnoli,” Bologna, Italy
- 19Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, South Korea
- 20Department of Internal Medicine, Isala Klinieken, Zwolle, The Netherlands
- 21Department of Hematology, St. Antonius Hospital Nieuwegein, Nieuwegein, Netherlands
- 22Department of Hematology and Transplantology, Medical University of Gdansk;, Poland
- 23Sahlgrenska University Hospital, Göteborg, Sweden
- 24The Lancashire Haematology Centre, Blackpool Teaching Hospitals NHS Foundation Trust, Blackpool Victoria Hospital, Blackpool, United Kingdom
- 25Stanford University School of Medicine, Palo Alto, California, United States
- 26Cancer Center Clínica Universidad de Navarra, University of Navarra, Pamplona, Spain
- 27Hematology Department, Hospital 12 de Octubre, Universidad Complutense, Spain
- 28Memorial Sloan Kettering Cancer Center, New York, United States
- 29Hematologic Malignancies and Cellular Therapy Program, Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, United States
- 30Hematology Unit, Istituto Romagnolo per lo Studio dei Tumori ''Dino Amadori, Italy
- 31Hematology, CHU Lille, University of Lille, France
- 32Cancer Center Clinica Universidad de Navarra, CIMA, IDISNA, Pamplona, Spain
- 33Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, United States
- 34Johnson & Johnson, Spring House, PA, United States
- 35Johnson & Johnson, Los Angeles, CA, United States
- 36Johnson & Johnson, Spring House, PA, United State
- 37Johnson & Johnson, High Wycombe, United Kingdom
- 38Johnson & Johnson, Yorba Linda, CA, United States
- 39Johnson & Johnson, Raritan, NJ, United States
- 40Johnson & Johnson, Shanghai, China
Abstract
Background: Tec-Dara demonstrated significant improvement in PFS (primary endpoint) and all key secondary endpoints (including ≥ CR, minimal residual disease [MRD] negativity [neg], and OS) vs Dara + dexamethasone + pomalidomide or bortezomib (DPd/DVd) in the primary analysis of the phase 3 MajesTEC-3 trial (NCT05083169) in early-line RRMM. PFS/OS favored Tec-Dara across all subgroups, and the safety profile was well-managed. Aims: We report in-depth, post-hoc subgroup analyses of MajesTEC-3 (PFS, MRD-neg CR rate) in pts with and without high-risk cytogenetic abnormalities (HRCAs) and functional high-risk (FHR) status. Methods: Pts had 1-3 prior lines of therapy (LOT) including a proteasome inhibitor and lenalidomide (lenalidomide refractory if only 1 prior LOT) with progressive disease (PD) on/after last LOT. Pts were randomized 1:1 to Tec-Dara or DPd/DVd. Tec-Dara pts received 28-day cycles (C) of Tec (C1-2: 1.5 mg/kg QW [C1 dose preceded by approved step-up dose schedule]; C3-6: 3 mg/kg Q2W; C7+: 3 mg/kg Q4W) with Dara; steroid-sparing after C1 Day 8. Tec and Dara dosing were aligned with the approved Dara schedule. DPd/DVd were administered per approved schedules. The prespecified definition of high risk included ≥ 1 of the following HRCAs: t(4;14), t(14;16), or del(17p); a revised high-risk definition also included gain(1q21) or amp(1q21) (3 and ≥ 4 copies, respectively). Risk subgroups reported include: standard (std.) or high (0 or ≥ 1 HRCAs, respectively, per prespecified definition); revised std. or high (0 or ≥ 1 HRCAs per revised definition); and 1 or ≥ 2 HRCAs (per revised definition). FHR was defined as 1 prior LOT with PD ≤ 18 mo post-ASCT or start of initial therapy. MRD-neg CR rate was defined as the percentage of pts in the NGS analysis set (all randomized pts except those in China [only NGF cytometry available]) who achieved both ≥ CR and MRD neg (10–5 or 10–6). Results: 587 pts were randomized (Tec-Dara, n = 291; DPd/DVd, n = 296). At 34.5 mo median follow-up, PFS favored Tec-Dara vs DPd/DVd across all cytogenetic subgroups (Figure). Estimated 36-mo PFS rates were higher with Tec-Dara vs DPd/DVd for both prespecified std. (87.4% vs 37.1%) and high-risk cytogenetics (77.7% vs 11.5%). Among pts with 1 prior LOT, PFS also favored Tec-Dara vs DPd/DVd both in pts with FHR (estimated 36-mo PFS rate, 77.3% vs 0%; HR, 0.22 [95% CI, 0.08-0.62]) and without FHR (89.9% vs 35.9%; HR, 0.11 [95% CI, 0.05-0.23]). MRD-neg CR rates were higher with Tec-Dara vs DPd/DVd across all risk subgroups: std. (10–5: 62.6% vs 24.8%; 10–6: 58.9% vs 14.7%; both P < 0.0001), high (57.9% vs 9.7%; 54.7% vs 5.4%; both P < 0.0001), revised std. (67.4% vs 18.8%; 67.4% vs 6.3%; both P<0.0001), revised high (57.5% vs 17.5%; 53.4% vs 11.3%; both P < 0.0001), 1 HRCA (53.9% vs 21.4%; 48.3% vs 14.3%; both P < 0.0001), ≥ 2 HRCAs (63.2% vs 11.3%; 61.4% vs 6.5%; both P<0.0001). MRD-neg CR rates were also higher with Tec-Dara in pts with FHR MM (10–5: 42.9% vs 5.6%, P = 0.0106; 10–6: 38.1% vs 0%, P = 0.0040). Additional data and high-risk subgroups will be presented. Conclusion: Tec-Dara substantially improved PFS and MRD-neg CR rates vs DPd/DVd regardless of cytogenetic risk and FHR status. The 36-mo PFS rates of 87.4% and 89.9% in pts with std. risk and non-FHR MM, respectively, and attenuation of the adverse prognosis associated with high-risk disease support Tec-Dara as a steroid-sparing standard-of-care as early as the 2nd LOT, across all practice settings and regardless of risk status.
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BibTeX
@article{banerjee2026teclistamab,
title = {{TECLISTAMAB PLUS DARATUMUMAB (TEC-DARA) IN PATIENTS (PTS) WITH RELAPSED REFRACTORY MULTIPLE MYELOMA (RRMM): ANALYSIS OF MAJESTEC-3 BASED ON CYTOGENETIC AND FUNCTIONAL RISK}},
author = {Rahul BANERJEE and Niels WCJ VAN DE DONK and Roberto MINA and Mateos MATEOS and Nizar J BAHLIS and Aurore PERROT and Ajay K NOOKA and Jin LU and Charlotte PAWLYN and Gaston CAEIRO and Alain KENTOS and Vania HUNGRIA and Anne K MYLIN and Charlotte TOFTMANN HANSEN and Raphael TEIPEL, and Britta BESEMER and Meletios A DIMOPOULOS and Elena ZAMAGNI and Satoshi YOSHIHARA and Kihyun KIM and Paul GEERTS and Elena VAN LEEUWEN-SEGARCEANU and Agata TYCZYNSKA and Markus HANSSON and Mark GREY and Surbhi SIDANA and Paula RODRIGUEZ-OTERO and Joaquin MARTINEZ-LOPEZ and Hamza HASHMI and Larry D. ANDERSON and Claudio CERCHIONE and Saloman MANIER and Jesús SAN-MIGUEL and Muhamed BALJEVIC and Robin CARSON and Weili SUN and Kristen LANTZ and Anne SEIFERT and Deborah BRISENO-TOOMEY and Lisa O'ROURKE and Maria RUBIN and Diego VIEYRA and Lijuan KANG and Hongmei XU and Ricardo ATTAR and Christopher CHIU and Luciano J COSTA},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.107938},
url = {https://doi.org/10.1016/j.htct.2026.107938},
note = {CC BY},
}
RIS
TY - JOUR
TI - TECLISTAMAB PLUS DARATUMUMAB (TEC-DARA) IN PATIENTS (PTS) WITH RELAPSED REFRACTORY MULTIPLE MYELOMA (RRMM): ANALYSIS OF MAJESTEC-3 BASED ON CYTOGENETIC AND FUNCTIONAL RISK
AU - Rahul BANERJEE
AU - Niels WCJ VAN DE DONK
AU - Roberto MINA
AU - Mateos MATEOS
AU - Nizar J BAHLIS
AU - Aurore PERROT
AU - Ajay K NOOKA
AU - Jin LU
AU - Charlotte PAWLYN
AU - Gaston CAEIRO
AU - Alain KENTOS
AU - Vania HUNGRIA
AU - Anne K MYLIN
AU - Charlotte TOFTMANN HANSEN
AU - Raphael TEIPEL,
AU - Britta BESEMER
AU - Meletios A DIMOPOULOS
AU - Elena ZAMAGNI
AU - Satoshi YOSHIHARA
AU - Kihyun KIM
AU - Paul GEERTS
AU - Elena VAN LEEUWEN-SEGARCEANU
AU - Agata TYCZYNSKA
AU - Markus HANSSON
AU - Mark GREY
AU - Surbhi SIDANA
AU - Paula RODRIGUEZ-OTERO
AU - Joaquin MARTINEZ-LOPEZ
AU - Hamza HASHMI
AU - Larry D. ANDERSON
AU - Claudio CERCHIONE
AU - Saloman MANIER
AU - Jesús SAN-MIGUEL
AU - Muhamed BALJEVIC
AU - Robin CARSON
AU - Weili SUN
AU - Kristen LANTZ
AU - Anne SEIFERT
AU - Deborah BRISENO-TOOMEY
AU - Lisa O'ROURKE
AU - Maria RUBIN
AU - Diego VIEYRA
AU - Lijuan KANG
AU - Hongmei XU
AU - Ricardo ATTAR
AU - Christopher CHIU
AU - Luciano J COSTA
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.107938
UR - https://doi.org/10.1016/j.htct.2026.107938
AB - Background: Tec-Dara demonstrated significant improvement in PFS (primary endpoint) and all key secondary endpoints (including ≥ CR, minimal residual disease [MRD] negativity [neg], and OS) vs Dara + dexamethasone + pomalidomide or bortezomib (DPd/DVd) in the primary analysis of the phase 3 MajesTEC-3 trial (NCT05083169) in early-line RRMM. PFS/OS favored Tec-Dara across all subgroups, and the safety profile was well-managed. Aims: We report in-depth, post-hoc subgroup analyses of MajesTEC-3 (PFS, MRD-neg CR rate) in pts with and without high-risk cytogenetic abnormalities (HRCAs) and functional high-risk (FHR) status. Methods: Pts had 1-3 prior lines of therapy (LOT) including a proteasome inhibitor and lenalidomide (lenalidomide refractory if only 1 prior LOT) with progressive disease (PD) on/after last LOT. Pts were randomized 1:1 to Tec-Dara or DPd/DVd. Tec-Dara pts received 28-day cycles (C) of Tec (C1-2: 1.5 mg/kg QW [C1 dose preceded by approved step-up dose schedule]; C3-6: 3 mg/kg Q2W; C7+: 3 mg/kg Q4W) with Dara; steroid-sparing after C1 Day 8. Tec and Dara dosing were aligned with the approved Dara schedule. DPd/DVd were administered per approved schedules. The prespecified definition of high risk included ≥ 1 of the following HRCAs: t(4;14), t(14;16), or del(17p); a revised high-risk definition also included gain(1q21) or amp(1q21) (3 and ≥ 4 copies, respectively). Risk subgroups reported include: standard (std.) or high (0 or ≥ 1 HRCAs, respectively, per prespecified definition); revised std. or high (0 or ≥ 1 HRCAs per revised definition); and 1 or ≥ 2 HRCAs (per revised definition). FHR was defined as 1 prior LOT with PD ≤ 18 mo post-ASCT or start of initial therapy. MRD-neg CR rate was defined as the percentage of pts in the NGS analysis set (all randomized pts except those in China [only NGF cytometry available]) who achieved both ≥ CR and MRD neg (10–5 or 10–6). Results: 587 pts were randomized (Tec-Dara, n = 291; DPd/DVd, n = 296). At 34.5 mo median follow-up, PFS favored Tec-Dara vs DPd/DVd across all cytogenetic subgroups (Figure). Estimated 36-mo PFS rates were higher with Tec-Dara vs DPd/DVd for both prespecified std. (87.4% vs 37.1%) and high-risk cytogenetics (77.7% vs 11.5%). Among pts with 1 prior LOT, PFS also favored Tec-Dara vs DPd/DVd both in pts with FHR (estimated 36-mo PFS rate, 77.3% vs 0%; HR, 0.22 [95% CI, 0.08-0.62]) and without FHR (89.9% vs 35.9%; HR, 0.11 [95% CI, 0.05-0.23]). MRD-neg CR rates were higher with Tec-Dara vs DPd/DVd across all risk subgroups: std. (10–5: 62.6% vs 24.8%; 10–6: 58.9% vs 14.7%; both P < 0.0001), high (57.9% vs 9.7%; 54.7% vs 5.4%; both P < 0.0001), revised std. (67.4% vs 18.8%; 67.4% vs 6.3%; both P<0.0001), revised high (57.5% vs 17.5%; 53.4% vs 11.3%; both P < 0.0001), 1 HRCA (53.9% vs 21.4%; 48.3% vs 14.3%; both P < 0.0001), ≥ 2 HRCAs (63.2% vs 11.3%; 61.4% vs 6.5%; both P<0.0001). MRD-neg CR rates were also higher with Tec-Dara in pts with FHR MM (10–5: 42.9% vs 5.6%, P = 0.0106; 10–6: 38.1% vs 0%, P = 0.0040). Additional data and high-risk subgroups will be presented. Conclusion: Tec-Dara substantially improved PFS and MRD-neg CR rates vs DPd/DVd regardless of cytogenetic risk and FHR status. The 36-mo PFS rates of 87.4% and 89.9% in pts with std. risk and non-FHR MM, respectively, and attenuation of the adverse prognosis associated with high-risk disease support Tec-Dara as a steroid-sparing standard-of-care as early as the 2nd LOT, across all practice settings and regardless of risk status.
SN - 2531-1379
SN - 2531-1387
ER -