• Yael C Cohen, Hila Magen, Moshe Gatt, Michael Sebag, Kihyun Kim, Chang-Ki Min, Enrique M Ocio, Sung-Soo Yoon, Michael P Chu, Paula Rodríguez-Otero, Irit Avivi, Natalia A Quijano Cardé, Ashwini Kumar, Maria Krevvata, Michelle R Peterson, Lilla Di Scala, Emma Scott, Brandi Hilder, Jill Vanak, Arnob Banerjee, Albert Oriol, Daniel Morillo, María-Victoria Mateos, and RedirecTT-1 Investigators and Study Group.
• From Tel Aviv Sourasky Medical Center (Y.C.C., I.A.), and the Faculty of Medical and Health Sciences, Tel Aviv University (Y.C.C., H.M., I.A.), Tel Aviv, Chaim Sheba Medical Center, Ramat Gan (H.M.), and Hadassah Hebrew University Medical Center, Jerusalem (M.G.) - all in Israel; McGill University and McGill University Health Centre, Montreal (M.S.), and Alberta Health Services, Edmonton (M.P.C.) - all in Canada; Samsung Medical Center, Sungkyunkwan University School of Medicine (K.K.), Seoul St. Mary's Hospital, Catholic University of Korea (C.-K.M.), and Seoul National University College of Medicine (S.-S.Y.) - all in Seoul, South Korea; Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Sanitaria Valdecilla, Universidad de Cantabria, Santander (E.M.O.), Cancer Center Clínica Universidad de Navarra, Center for Applied Medical Research, Pamplona (P.R.-O.), Institut Català d'Oncologia, Josep Carreras Leukemia Research Institute, and the Hospital Germans Trias i Pujol, Barcelona (A.O.), START Madrid-Fundación Jiménez Díaz Early Phase Unit, University Hospital Fundación Jiménez Díaz, Madrid (D.M.), and the University Hospital of Salamanca, Institute for Biomedical Research of Salamanca, the Salamanca Cancer Research Center, and Centro de Investígación Biomédica en Red Cáncer, Salamanca (M.-V.M.) - all in Spain; Janssen Research and Development, Spring House, PA (N.A.Q.C., A.K., M.K., M.R.P., E.S., B.H., J.V., A.B.); and Janssen Research and Development, Allschwil, Switzerland (L.D.S.).
• N. Engl. J. Med. 2025 Jan 9; 392 (2): 138149138-149.

BackgroundTalquetamab (anti-G protein-coupled receptor family C group 5 member D) and teclistamab (anti-B-cell maturation antigen) are bispecific antibodies that activate T cells by targeting CD3 and that have been approved for the treatment of triple-class-exposed relapsed or refractory multiple myeloma.MethodsWe conducted a phase 1b-2 study of talquetamab plus teclistamab in patients with relapsed or refractory multiple myeloma. In phase 1, we investigated five dose levels in a dose-escalation study. Talquetamab at a dose of 0.8 mg per kilogram of body weight plus teclistamab at a dose of 3.0 mg per kilogram every other week was selected as the recommended phase 2 regimen. The primary objective was to evaluate adverse events and dose-limiting toxic effects.ResultsA total of 94 patients received treatment, with the recommended phase 2 regimen used in 44. The median follow-up was 20.3 months. Three patients had dose-limiting toxic effects (including grade 4 thrombocytopenia in 1 patient with the recommended phase 2 regimen). Across all dose levels, the most common adverse events were cytokine release syndrome, neutropenia, taste changes, and nonrash skin events. Grade 3 or 4 adverse events, most commonly hematologic events, occurred in 96% of the patients. Grade 3 or 4 infections occurred in 64% of the patients. With the recommended phase 2 regimen, a response occurred in 80% of the patients (including in 61% of those with extramedullary disease); across all dose levels, a response occurred in 78%. The likelihood of patients continuing in response at 18 months was 86% with the recommended phase 2 regimen (82% among those with extramedullary disease) and 77% across all dose levels.ConclusionsThe incidence of grade 3 or 4 infections with talquetamab plus teclistamab was higher than has been observed with either therapy alone. A response was observed in a high percentage of patients across all dose levels, with durable responses with the recommended phase 2 regimen. (Funded by Janssen Research and Development; RedirecTT-1 ClinicalTrials.gov number, NCT04586426.).Copyright © 2025 Massachusetts Medical Society.

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