1. Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma.
- Author
-
Cohen YC, Magen H, Gatt M, Sebag M, Kim K, Min CK, Ocio EM, Yoon SS, Chu MP, Rodríguez-Otero P, Avivi I, Quijano Cardé NA, Kumar A, Krevvata M, Peterson MR, Di Scala L, Scott E, Hilder B, Vanak J, Banerjee A, Oriol A, Morillo D, and Mateos MV
- Subjects
- Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Dose-Response Relationship, Drug, Maximum Tolerated Dose, Recurrence, Drug Resistance, Neoplasm, Treatment Outcome, Antibodies, Bispecific administration & dosage, Antibodies, Bispecific adverse effects, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Antineoplastic Combined Chemotherapy Protocols adverse effects, B-Cell Maturation Antigen antagonists & inhibitors, Multiple Myeloma diagnosis, Multiple Myeloma drug therapy, Receptors, G-Protein-Coupled antagonists & inhibitors, Neoplasm Recurrence, Local diagnosis, Neoplasm Recurrence, Local drug therapy
- Abstract
Background: Talquetamab (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., Methods: We 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., Results: A 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., Conclusions: The 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.)
- Published
- 2025
- Full Text
- View/download PDF