Article (Scientific journals)
Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma.
Chari, Ajai; Minnema, Monique C; Berdeja, Jesus G et al.
2022In New England Journal of Medicine, 387 (24), p. 2232-2244
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Keywords :
Antibodies, Bispecific; GPRC5D protein, human; Receptors, G-Protein-Coupled; CD3 Complex; Humans; Antibodies, Bispecific/administration & dosage/adverse effects/immunology/therapeutic use; Cytokine Release Syndrome/chemically induced/etiology; Dysgeusia/chemically induced/etiology; Multiple Myeloma/drug therapy/immunology/therapy; Neoplasm Recurrence, Local/drug therapy; Receptors, G-Protein-Coupled/antagonists & inhibitors/immunology; T-Lymphocytes/drug effects/immunology; CD3 Complex/antagonists & inhibitors/immunology; Administration, Intravenous; Injections, Subcutaneous; Skin Diseases/chemically induced/etiology
Abstract :
[en] BACKGROUND: G 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. METHODS: In 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. RESULTS: At 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. CONCLUSIONS: Cytokine 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.).
Disciplines :
Hematology
Author, co-author :
Chari, Ajai;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Minnema, Monique C;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Berdeja, Jesus G;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Oriol, Albert;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
van de Donk, Niels W C J;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Rodríguez-Otero, Paula;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Askari, Elham;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Mateos, María-Victoria;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Costa, Luciano J ;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Caers, Jo  ;  Centre Hospitalier Universitaire de Liège - CHU > > Service d'hématologie clinique ; From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Verona, Raluca;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Girgis, Suzette;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Yang, Shiyi;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Goldsmith, Rachel B;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Yao, Xiang;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Pillarisetti, Kodandaram;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Hilder, Brandi W;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Russell, Jeffery;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Goldberg, Jenna D;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
Krishnan, Amrita;  From the Mount Sinai School of Medicine, New York (A.C.), University Medical
More authors (10 more) Less
Language :
English
Title :
Talquetamab, a T-Cell-Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma.
Publication date :
15 December 2022
Journal title :
New England Journal of Medicine
ISSN :
0028-4793
eISSN :
1533-4406
Publisher :
Massachusetts Medical Society, Us ma
Volume :
387
Issue :
24
Pages :
2232-2244
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright © 2022 Massachusetts Medical Society.
Available on ORBi :
since 03 January 2023

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