Talquetamab–Daratumumab in Relapsed or Refractory Myeloma

作者：Roberto Mina, Meral Beksac, Paula Rodríguez‐Otero, Wenming Chen, María-Victoria Mateos, Jian Li, Philippe Moreau, Yaël Cohen, Chang‐Ki Min, Tomáš Jelı́nek, Jing Christine Ye, Hila Magen, Samuel M. Rubinstein, Weijun Fu, Vania Hungria, Guldane Cengiz Seval, Joao Samuel Farias, Jakub Radocha, Senem Maral, Mehmet Turgut, Youngil Koh, Daniel OʼLeary, Jayr Schmidt Filho, Raymond Thertulien, Gang An, Shang‐Yi Huang, Sebastian Grosicki, Agata Tyczyńska, Rahul Banerjee, Matthew J. Pianko, Joaquín Martínez‐López, Paweł Steckiewicz, Dai Maruyama, Kentaro Fukushima, Albert Oriol, Jordi López Pardo, Hartmut Goldschmidt, Charlotte Pawlyn, Aurore Perrot, Elena Zamagni, Meletios A. Dimopoulos, Leo Rasche, Jaszianne Tolbert, William Terry, Christelle Courtoux, Xiao Liu, Sandra Y. Vasey, Kaitlyn Connors, M Festa, Christoph Heuck, Angélique Langlois, Lisa O’Rourke, Jiangxiu Zhou, Xiang Qin, Jiashen Lu, Joy Gong, Diego Vieyra, Peter M. Voorhees · 发表于：New England Journal of Medicine · 年份：2026 · DOI：10.1056/nejmoa2604657 · 被引用次数：6 · 研究领域：Multiple Myeloma Research and Treatments、Neuroblastoma Research and Treatments、Lung Cancer Research Studies

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 at 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. RESULTS: A total of 287, 287, and 290 patients were assigned to the Tal-DP, Tal-D, and DPd groups, respectively. At 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<0.001 for both comparisons). 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...