Behind the RedirecTT-1 Study in Multiple Myeloma With EMD

Shahzad Raza, MD, hematologist/oncologist at the Cleveland Clinic, discusses the phase 2 RedirecTT-1 study (NCT04586426) which investigated the combination of talquetamab (Talvey) and teclistamab (Tecvaylo) for treating patients with relapsed/refractory multiple myeloma (RRMM) complicated by extramedullary disease (EMD).

The trial enrolled 90 heavily pretreated patients, with 84.4% triple-class refractory and 35.6% penta-drug refractory. Notably, 20% had prior chimeric antigen receptor T-cell therapy, and patients with non-secretory or oligo-secretory disease were included, populations often excluded from other studies. After a median follow-up of 12.6 months, the combination therapy achieved an overall response rate (ORR) of 78.9%, with 54.4% of patients attaining a complete response or better. Raza described these outcomes as unprecedented, particularly compared to monotherapy EMD response rates, which typically hover around 43%.

The responses were durable, with 66.2% of responders maintaining their remission at data cutoff. The median duration of response was 13.8 months, and 61% of patients remained progression-free and alive at one year. Overall survival data are promising, with 74.5% alive at one year and median survival not yet reached.

Talquetamab and teclistamab are bispecific antibodies targeting GPRC5D and BCMA, respectively. Their combination shows powerful synergy, overcoming resistance mechanisms common in EMD. The treatment regimen included initial step-up dosing followed by dosing every two weeks, transitioning to monthly dosing after deep responses were achieved.

Importantly, the combination therapy was well tolerated. Cytokine release syndrome (CRS) was mostly grade 1 or 2, manageable with standard interventions. Immune effector cell-associated neurotoxicity syndrome (ICANS) was rare, occurring in approximately 4% of patients. Toxicities were consistent with those seen in single-agent therapy, alleviating concerns about increased adverse effects with the combination.

These findings were presented at the 2025 European Hematology Association Congress and highlight the promising role of talquetamab plus teclistamab in this challenging RRMM population with EMD.

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