• Ajai Chari, Monique C Minnema, Jesus G Berdeja, Albert Oriol, van de DonkNiels W C JNWCJFrom the Mount Sinai School of Medicine, New York (A.C.); University Medical Center Utrecht, Utrecht University, Utrecht (M.C.M.), and Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Am, Paula Rodríguez-Otero, Elham Askari, María-Victoria Mateos, Luciano J Costa, Jo Caers, Raluca Verona, Suzette Girgis, Shiyi Yang, Rachel B Goldsmith, Xiang Yao, Kodandaram Pillarisetti, Brandi W Hilder, Jeffery Russell, Jenna D Goldberg, and Amrita Krishnan.
• From the Mount Sinai School of Medicine, New York (A.C.); University Medical Center Utrecht, Utrecht University, Utrecht (M.C.M.), and Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Amsterdam (N.W.C.J.D.) - both in the Netherlands; Sarah Cannon Research Institute and Tennessee Oncology, Nashville (J.G.B.); Institut Català d'Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona, Barcelona (A.O.), Clínica Universidad de Navarra, Pamplona (P.R.-O.), Hospital Universitario Fundación Jiménez Díaz, Madrid (E.A.), and University Hospital of Salamanca, Instituto de Investigación Biomédica de Salamanca, Centro de Investigación del Cáncer, Centro de Investigación Biomédica en Red de Cáncer, Salamanca (M.-V.M.) - all in Spain; the University of Alabama at Birmingham, Birmingham (L.J.C.); Centre Hospitalier Universitaire de Liège, Liege, Belgium (J.C.); Janssen Research and Development, Spring House, PA (R.V., S.G., S.Y., R.B.G., K.P., B.W.H., J.R.); Janssen Research and Development, La Jolla (X.Y.), and City of Hope Comprehensive Cancer Center, Duarte (A.K.) - both in California; and Janssen Research and Development, Raritan, NJ (J.D.G.).
• N. Engl. J. Med. 2022 Dec 15; 387 (24): 223222442232-2244.

BackgroundG protein-coupled receptor, family C, group 5, member D (GPRC5D) is an orphan receptor expressed in malignant plasma cells. Talquetamab, a bispecific antibody against CD3 and GPRC5D, redirects T cells to mediate killing of GPRC5D-expressing myeloma cells.MethodsIn a phase 1 study, we evaluated talquetamab administered intravenously weekly or every other week (in doses from 0.5 to 180 μg per kilogram of body weight) or subcutaneously weekly, every other week, or monthly (5 to 1600 μg per kilogram) in patients who had heavily pretreated relapsed or refractory multiple myeloma that had progressed with established therapies (a median of six previous lines of therapy) or who could not receive these therapies without unacceptable side effects. The primary end points - the frequency and type of dose-limiting toxic effects (study part 1 only), adverse events, and laboratory abnormalities - were assessed in order to select the recommended doses for a phase 2 study.ResultsAt the data-cutoff date, 232 patients had received talquetamab (102 intravenously and 130 subcutaneously). At the two subcutaneous doses recommended for a phase 2 study (405 μg per kilogram weekly [30 patients] and 800 μg per kilogram every other week [44 patients]), common adverse events were cytokine release syndrome (in 77% and 80% of the patients, respectively), skin-related events (in 67% and 70%), and dysgeusia (in 63% and 57%); all but one cytokine release syndrome event were of grade 1 or 2. One dose-limiting toxic effect of grade 3 rash was reported in a patient who had received talquetamab at the 800-μg dose level. At median follow-ups of 11.7 months (in patients who had received talquetamab at the 405-μg dose level) and 4.2 months (in those who had received it at the 800-μg dose level), the percentages of patients with a response were 70% (95% confidence interval [CI], 51 to 85) and 64% (95% CI, 48 to 78), respectively. The median duration of response was 10.2 months and 7.8 months, respectively.ConclusionsCytokine release syndrome, skin-related events, and dysgeusia were common with talquetamab treatment but were primarily low-grade. Talquetamab induced a substantial response among patients with heavily pretreated relapsed or refractory multiple myeloma. (Funded by Janssen Research and Development; MonumenTAL-1 ClinicalTrials.gov number, NCT03399799.).Copyright © 2022 Massachusetts Medical Society.

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