Talquetamab–Daratumumab in Relapsed or Refractory Myeloma

Author(s): Roberto Mina, M.D.1,2; Meral Beksac, M.D.3; Paula Rodríguez-Otero, M.D., Ph.D.4; Wenming Chen, M.D., Ph.D.5; María-Victoria Mateos, M.D., Ph.D.6; Jian Li, M.D.7; Philippe Moreau, M.D.8; Yael C. Cohen, M.D.9,10; Chang-Ki Min, M.D., Ph.D.11; Tomas Jelinek, M.D., Ph.D.12; Jing Christine Ye, M.D.13; Hila Magen, M.D.14,15; Samuel M. Rubinstein, M.D.16; Weijun Fu, M.D., Ph.D.17; Vania Hungria, M.D., Ph.D.18; Guldane Cengiz Seval, M.D.19; Joao Samuel Farias, M.D.20; Jakub Radocha, M.D.21; Senem Maral, M.D.22; Mehmet Turgut, M.D., Ph.D.23; Youngil Koh, M.D., Ph.D.24; Daniel O’Leary, M.D.25; Jayr Schmidt Filho, M.D.26; Raymond Thertulien, M.D., Ph.D.27; Gang An, M.D., Ph.D.28; Shang-Yi Huang, M.D., Ph.D.29; Sebastian Grosicki, M.D.30; Agata Tyczyńska, M.D., Ph.D.31; Rahul Banerjee, M.D.32; Matthew J. Pianko, M.D.33; Joaquín Martínez-López, M.D., Ph.D.34; Pawel Steckiewicz, M.D., Ph.D.35; Dai Maruyama, M.D., Ph.D.36; Kentaro Fukushima, M.D., Ph.D.37; Albert Oriol, M.D., Ph.D.38; Jordi Lopez Pardo, M.D.39; Hartmut Goldschmidt, M.D.40; Charlotte Pawlyn, M.D., Ph.D.41,42; Aurore Perrot, M.D., Ph.D.43; Elena Zamagni, M.D., Ph.D.44; Meletios A. Dimopoulos, M.D.45,46; Leo Rasche, M.D.47; Jaszianne Tolbert, M.D.48; William Terry, M.D.48; Christelle Courtoux, M.Eng.48; Xiao Liu, M.D.49; Sandra Y. Vasey, M.S.48; Kaitlyn Connors, B.S.50; Mariacristina Festa, M.S.51; Christoph Heuck, M.D.48; Angélique Langlois, M.Sc.48; Lisa O’Rourke, M.S.48; Jiangxiu Zhou, Ph.D.48; Xiang Qin, M.S.48; Jiashen Lu, Ph.D.52; Joy Gong, Ph.D.48; Diego Vieyra, Ph.D.48; Peter M. Voorhees, M.D.53; the MonumenTAL-3 Investigators*;
Source: DOI: 10.1056/NEJMoa2604657
Original Article
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A total of 287, 287, and 290 patients were assigned to the Tal-DP, (tal with dara and pomalidomide) Tal-D(Tal with dara) , and DPd (dara, pom and dex) groups, respectively. Progression-free survival (PFS) was 81.3% for TalDP and 77.6 % for Tal D compared to 51.2% for DPd. The overall response was higher with Tal-DP and Tal-D than with DPd (88.2% and 88.5% vs. 77.6%), as was complete response or better (71.1% and 69.0% vs. 34.5%) and measurable residual disease–negative complete response (52.3% and 46.3% vs. 15.9%) (P<0.001 for all comparisons). Overall survival at 24 months was 89.2% with Tal-DP, 87.9% with Tal-D, and 79.1% with DPd. Tal DP had less fatality secondary to adverse events (1.8%) vs Tal d 4% and DPd 4.6%. We will see more studies with cellular therapy combinations now and it seems promising, esp. with better control of toxicity.

BACKGROUND

Talquetamab, a bispecific antibody targeting GPRC5D and CD3, has led to durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma in phase 1–2 trials, with a limited effect on normal B cells.

METHODS

In a phase 3 trial, we randomly assigned patients with relapsed or refractory multiple myeloma who had previously received least one line of therapy to receive talquetamab plus daratumumab and pomalidomide (Tal-DP), talquetamab plus daratumumab (Tal-D), or daratumumab plus pomalidomide and dexamethasone (DPd). The primary end point was progression-free survival as assessed by an independent review committee. Key secondary end points were overall response, complete response or better (complete or stringent complete response), measurable residual disease–negative complete response, and overall survival. Research Summary Talquetamab–Daratumumab in Relapsed or Refractory Myeloma

RESULTS

A total of 287, 287, and 290 patients were assigned to the Tal-DP, Tal-D, and DPd groups, respectively. the interim analysis (median follow-up, 24.6 months), progression-free survival was significantly longer with Tal-DP and Tal-D than with DPd (24-month estimate, 81.3% and 77.6% vs. 51.2%; hazard ratio for disease progression or death, Tal-DP vs. DPd, 0.28 [95% confidence interval {CI}, 0.20 to 0.40], and Tal-D vs. DPd, 0.33 [95% CI, 0.24 to 0.46]; P

CONCLUSIONS

Among patients with relapsed or refractory multiple myeloma who had previously received least one line of therapy, both Tal-DP and Tal-D led to significantly longer progression-free survival than DPd. (Funded by Johnson & Johnson; MonumenTAL-3 ClinicalTrials.gov number, NCT05455320.) Quick Take Talquetamab Combinations in Relapsed or Refractory Myeloma 2m 35s

Author Affiliations

1Division of Hematology, Department of Molecular Biotechnology and Health Sciences, Azienda Ospedaliero-Universitaria Città della Salute e della, Scienza di Torino, University of Turin, Turin, Italy; 2Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta; 3Istinye University, Ankara University, Ankara, Turkey; 4Cancer Center Clínica Universidad de Navarra, Cima, Pamplona, Spain; 5Beijing Chaoyang Hospital, Capital Medical University, Chaoyang District, Beijing; 6Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Instituto de Biología Molecular y Celular del Cáncer (Universidad de Salamanca-Consejo Superior de Investigaciones Científicas), Centro de Investigación Biomédica en Red de Cáncer, Salamanca, Spain; 7Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing; 8Hematology Clinic, University Hospital Hôtel-Dieu, Nantes, France; 9Tel Aviv Sourasky (Ichilov) Medical Center, Tel Aviv, Israel; 10Gray Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel; 11Seoul St. Mary’s Hospital, Catholic University of Korea, Seoul, South Korea; 12Department of Hemato-oncology, University Hospital Ostrava, Ostrava, Czech Republic; 13M.D. Anderson Cancer Center, University of Texas, Houston; 14Chaim Sheba Medical Center, Ramat-Gan, Israel; 15Sackler Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv, Israel; 16Division of Hematology and Oncology, Department of Medicine, University of North Carolina School of Medicine, Chapel Hill; 17Department of Hematology, Shanghai Fourth People’s Hospital, School of Medicine, Tongji University, Shanghai; 18Clinica Médica São Germano, São Paulo; 19Ankara University Faculty of Medicine, Department of Hematology and Oncology, Ankara University, Ankara, Turkey; 20Liga Paranaense de Combate ao Câncer, Curitiba, Paraná, Brazil; 214th Department of Internal Medicine–Hematology, University Hospital Hradec Kralove, Faculty of Medicine in Hradec Kralove, Charles University, Prague, Czech Republic; 22Medipol Mega University Hospital, Bağcılar, Istanbul, Turkey; 23Ondokuz Mayıs University, Samsun, Turkey; 24Seoul National University Hospital, Seoul National University, Jongno-gu, Seoul, South Korea; 25University of Minnesota, Minneapolis; 26A.C.Camargo Cancer Center, São Paulo; 27Novant Health Cancer Institute, Charlotte, NC; 28Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, Tianjin, China; 29National Taiwan University Hospital, National Taiwan University College of Medicine, Zhongzheng District, Taipei; 30Department of Cancer Prevention, Medical University of Silesia, Katowice, Poland; 31Medical University of Gdańsk, Department of Hematology and Transplantology and University Clinical Center Gdańsk, Department of Hematology, Transplantology and Cellular Therapies, Gdańsk, Poland; 32Fred Hutchinson Cancer Center, Seattle; 33University of Michigan Health, Ann Arbor; 34Hospital Universitario 12 de Octubre, Instituto de Investigación Sanitaria Hospital 12 de Octubre, Complutense University of Madrid, Centro Nacional de Investigaciones Oncológicas, Madrid Institute of Cancer, Madrid; 35Holy Cross Cancer Center, Department of Hematology and Bone Marrow Transplantation, Kielce, Poland; 36Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo; 37University of Osaka Graduate School of Medicine, Suita, Japan; 38Institut Català d’Oncologia and Josep Carreras Research Institute, Hospital Germans Trias I Pujol, Badalona, Barcelona; 39l’Hospital de la Santa Creu i Sant Pau, Barcelona; 40Internal Medicine V, Hematology, Oncology and Rheumatology, German-Speaking Myeloma Multicenter Group Study Group, Heidelberg University Hospital and National Center for Tumor Diseases, Heidelberg, Germany; 41Institute of Cancer Research, London; 42Royal Marsden NHS Foundation Trust, London; 43Universite de Toulouse, Centre Hospitalier Universitaire de Toulouse, Service Hematologie, Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France; 44University of Bologna, Bologna, Italy; 45Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens; 46Department of Medicine, Korea University, Seoul, South Korea; 47University Hospital of Würzburg, Würzburg, Germany; 48Johnson & Johnson, Spring House, PA; 49Johnson & Johnson, Beijing; 50Johnson & Johnson, Raritan, NJ; 51Johnson & Johnson, Leiden, the Netherlands; 52Johnson & Johnson, Shanghai; 53Atrium Health Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, NC

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