Multinational phase 2 trial of talquetamab plus teclistamab for extramedullary myeloma

Patients with plasmacytomas that are noncontiguous with bone marrow (true extramedullary myeloma) are at high risk for disease progression or relapse. Phase 2 of the multinational phase1-2 RedirecTT-1 trial evaluated 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. The primary endpoint was overall response, evaluated with the use of functional imaging. The study included 90 patients, with a median follow-up of 12.6 months. A response occurred in 79% of the patients (95% CI 69-87). Among the patients with a response, the percentage with response duration of at least 12 months was 64% (95% CI 48-76). At 12 months, progression-free survival rate was 61% (95% CI 50-71) and overall survival rate was 74% (63-83). Grade 3 or 4 adverse events occurred in 76% of the patients; 31% had grade 3 or 4 infection. Nonfatal adverse events led to discontinuation of one or both agents in 6% of 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. The authors conclude that most patients with drug-resistant, true extramedullary myeloma had a response with talquetemab plus teclistamab. The incidence of adverse events of grade 3 and above was high and was consistent with previous observation for each agent as monotherapy.