Talquetamab/Teclistamab Combo Shows High, Durable Responses in RRMM With EMD

Shahzad Raza, MD, hematologist/oncologist at the Cleveland Clinic, discusses new data from the phase 2 RedirecTT-1 study (NCT04586426) of talquetamab (Talvey) with teclistamab (Tecvaylo) for the treatment of patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD).

EMD, characterized by myeloma cells forming soft tissue plasmacytomas outside the bone marrow, typically carries a poor prognosis. Raza emphasized the study's strict definition of EMD: "We define the EMD very differently... basically, we wanted 1 or more non-radiated, bone-independent soft tissue plasmacytomas, 2 cm or more in the greatest dimension, which is confirmed by the PET CT." This ensured the focus was on true extramedullary involvement.

The 90 patients in RedirecTT-1 were heavily pretreated, with 84.4% being triple-class refractory and 35.6% penta-drug refractory. The trial was notably inclusive, allowing patients with prior chimeric antigen receptor T-cell therapy (20%) and those with non-secretory or oligo-secretory disease, who are often excluded from other trials.

With a median follow-up of 12.6 months (range, 0.5-19.5), the combination achieved an overall response rate (ORR) of 78.9%. More than half of the patients (54.4%) reached a complete response or better. Raza called these findings "very unprecedented," noting it's "never been seen in the past by combining the 2 together." He highlighted the stark contrast to monotherapy, where EMD response rates are typically around 43%, stating, "With the combination in EMD, you are seeing close to 80% response rates. Very impressive results.”

These deep responses also proved durable. Among responders, 66.2% maintained their response at data cutoff. The median duration of response was 13.8 months, with 61% of patients remaining progression-free and alive at 1 year. Encouragingly, 74.5% of patients were alive at 1 year, and median overall survival has not yet been reached.

Talquetamab (GPRC5D-targeting) and teclistamab (BCMA-targeting) are both bispecific antibodies. Their combination appears to create a powerful synergy, effectively overcoming resistance mechanisms in EMD, according to findings presented at the 2025 European Hematology Association Congress.

REFERENCE:

Kumar S, Mateos MV, Ye JC, et al. Phase 2 study of talquetamab + teclistamab in patients with relapsed/refractory multiple myeloma and extramedullary disease: REDIRECTT-1. Presented at: European Hematology Association Congress; June 12-15, 2025; Milan, Italy. LBA4001