In a phase II trial (RedirecTT-1) reported in The New England Journal of Medicine, Kumar et al found that the combination of talquetamab (anti–G protein–coupled receptor family C group 5 member D) and teclistamab (anti–B-cell maturation antigen) produced high response rates in patients with drug-resistant, true extramedullary myeloma (plasmacytomas noncontiguous with bone marrow).
Study Details
Patients were enrolled in the international study between July 2023 and September 2024. By March 2025, a total of 90 patients had received treatment consisting of subcutaneous talquetamab at 0.8 mg/kg plus teclistamab at 3.0 mg/kg every other week in 28-day cycles after a dose step-up period. Patients had received a median of four prior lines of treatment (range = 1–10). The primary outcome measure was overall response (partial response or better).
Key Findings
Median follow-up was 12.6 months (range = 0.5–19.5 months). Among the 90 patients, 49 (54%) were still receiving treatment at data cutoff for the analysis, including 2 who were receiving only teclistamab.
Partial response or better was observed in 71 patients (79%, 95% confidence interval [CI] = 69%–87%), exceeding the hypothesized response rate of 40%. Very good partial response or better occurred in 63 patients (70%, 95% CI = 59%–79%), and complete response or better occurred in 49 (54%, 95% CI = 44%–65%). Median duration of response was 13.8 months (95% CI = 11.5 months to not estimable), with 64% of responses persisting for at least 12 months.
Median progression-free survival was 15.4 months (95% CI = 10.8 months to not estimable), with a 12-month rate of 61%. Median overall survival was not reached, with a 12-month rate of 74%.
Grade 3 or 4 adverse events occurred in 76% of patients, most commonly hematologic events (eg, neutropenia in 62%); grade 3 or 4 infection occurred in 31%. Oral adverse events of any grade occurred in 87% of patients. Cytokine-release syndrome, all grade 1 or 2, occurred in 78% of patients. Death considered related to treatment occurred in five patients (due to COVID-19–related pneumonia, klebsiella pneumonia, unspecified pneumonia, pseudomonal sepsis, and aspiration in one patient each).
The investigators concluded: “Most patients with drug-resistant, true extramedullary myeloma had a response with talquetamab plus teclistamab. The incidence of adverse events of grade 3 or above was high and was consistent with previous observations for each agent as monotherapy.”
Shaji Kumar, MD, of Mayo Clinic Rochester, Rochester, Minnesota, is the corresponding author for The New England Journal of Medicine article.
DISCLOSURE: The study was funded by Johnson & Johnson. For full disclosures of the study authors, visit nejm.org.
