EHA 2025 Data Updates: RedirecTT-1 -Talquetamab + Teclistamab

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The RedirecTT-1 trial evaluated the combination of talquetamab (GPRC5D-targeted) plus teclistamab (B-cell maturation antigen-targeted) in patients with heavily pretreated relapsed/refractory multiple myeloma, establishing recommended phase 2 dosing of 0.8 mg/kg talquetamab plus 3 mg/kg teclistamab administered biweekly. The study notably included a large cohort of patients with EMD, defined as greater than or equal to 2 cm lesions away from bone. Among 90 patients in the EMD-enriched cohort, 79% achieved overall responses, with particularly impressive 83% response rates in patients with prior chimeric antigen receptor T-cell therapy exposure.

Efficacy outcomes demonstrated durable responses with 9-month progression-free survival, duration of response, and overall survival rates of 65%, 75%, and 80%, respectively. The combination showed superior efficacy compared with single-agent bispecifics in patients with EMD, where teclistamab alone achieved 35% response rates and talquetamab achieved 40% response rates. Patients transitioning from biweekly to monthly dosing typically experienced response deepening without disease progression, suggesting potential for treatment de-escalation in responding patients.

Safety profiles reflected the additive toxicities of both agents, with 80% cytokine release syndrome incidence, 12% immune effector cell-associated neurotoxicity syndrome, and high rates of GPRC5D-related toxicities (70% skin, 60% nail). Infection rates were substantial (80% any grade, 40% grade 3 to 4), resulting in 10 deaths, including 5 treatment-related fatalities. The NCCN guidelines now include this combination as "useful in certain circumstances" after 3 prior lines of therapy, facilitating insurance approval for this challenging patient population.