Dual Targeting of Extramedullary Myeloma with Talquetamab and Teclistamab

BACKGROUND: Patients with plasmacytomas that are noncontiguous with bone marrow (true extramedullary myeloma) are at high risk for disease progression or relapse. Phase 1 of the RedirecTT-1 study showed promising efficacy with dual-antigen targeting of myeloma with talquetamab (anti-G protein-coupled receptor family C group 5 member D) plus teclistamab (anti-B-cell maturation antigen) in patients with triple-class-exposed relapsed or refractory multiple myeloma, including those with true extramedullary myeloma. METHODS: In this phase 2 study, we investigated talquetamab plus teclistamab exclusively in patients with drug-resistant, true extramedullary myeloma. The primary end point was overall response, evaluated with the use of functional imaging. Secondary end points included the duration of response, progression-free survival, overall survival, and safety. RESULTS: A total of 90 patients were enrolled in the study and received treatment (median follow-up, 12.6 months). A response occurred in 79% of the patients (95% confidence interval [CI], 69 to 87). Among the patients with a response, the percentage with a response duration of at least 12 months was 64% (95% CI, 48 to 76). At 12 months, progression-free survival was 61% (95% CI, 50 to 71), and overall survival was 74% (95% CI, 63 to 83). Common adverse events of any grade included oral symptoms, such as dysgeusia, dry mouth, and dysphagia (in 87% of the patients); cytokine release syndrome (in 78%); and nonrash skin effects (in 69%). Grade 3 or 4 adverse events (most commonly hematologic events) occurred in 76% of the patients; 31% had grade 3 or 4 infection. A nonfatal adverse event led to discontinuation of one or both agents in 6% of the patients. Among 10 deaths that occurred during follow-up, 5 were due to infection and 5 were considered to be related to the study treatment. CONCLUSIONS: 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. (Funded by Johnson & Johnson; RedirecTT-1 ClinicalTrials.gov number, NCT04586426.).