In a phase Ib-II study (RedirecTT-1) reported in The New England Journal of Medicine, Cohen et al found that the combination of the bispecific antibodies talquetamab (anti–G protein-coupled receptor family C group 5 member D) and teclistamab (anti–B-cell maturation antigen) was associated with a high risk of infection and high response rates in patients with triple class-exposed relapsed or refractory multiple myeloma.
Study Details
Ninety-four patients from sites in Canada, Israel, South Korea, and Spain were enrolled in the trial between December 2020 and April 2023. The phase I dose-escalation portion evaluated five dose levels of the combination. Talquetamab at 0.8 mg/kg plus teclistamab at 3.0 mg/kg every other week was selected as the recommended phase II regimen.
Key Findings
Median follow-up was 20.3 months. Among the 94 patients receiving treatment, 44 received the recommended phase II regimen.
Dose-limiting toxicity was observed in three patients, consisting of grade 3 elevated alanine aminotransferase and aspartate aminotransferase levels in one patient each and grade 4 thrombocytopenia in a patient receiving the recommended phase II dose level.
Across all dose levels, the most common adverse events of any grade were cytokine-release syndrome (79%), neutropenia (73%), taste changes (65%), and nonrash skin events (61%). Grade 3 or 4 adverse events, most commonly hematologic events, occurred in 96% of patients. Grade 3 or 4 infections occurred in 60 patients (64%). Infection led to death in 11 patients (12%).
At the recommended phase II regimen, response was observed in 80% of patients (including 61% of those with extramedullary disease), including very good partial response or better in 78% and complete response or better in 52%. At all dose levels, response was observed in 78% of patients, including very good partial response or better in 75% and complete response or better in 48%. The likelihood of patients continuing response at 18 months was 86% at the recommended phase II regimen (82% among those with extramedullary disease) and 77% across all dose levels.
The investigators concluded, “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 II regimen.”
Yael C. Cohen, MD, of Tel Aviv Sourasky Medical Center, Israel, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by Janssen Research and Development. For full disclosures of the study authors, visit nejm.org.
