Talquetamab Plus Teclistamab Demonstrates Durable Efficacy for Patients With R/R MM and Extramedullary Disease: Updated Results from RedirecTT-1 Study
Key Clinical Summary
- Population and Design: Phase 2 RedirecTT-1 trial evaluated talquetamab (0.8 mg/kg) plus teclistamab (3.0 mg/kg) every 2 weeks in 90 triple-class exposed relapsed/refractory MM patients with true extramedullary disease (EMD); median follow-up 16.2 months.
- Efficacy: ORR 77.8% (95% CI, 67.8 to 85.9) and CR ≥50%; 12-month DOR 60.1%, PFS 55.6%, OS 73.8%. Responses were strongest in patients with EMD tumor volume <25 cm² (ORR 90.7%, CR ≥ 60.5%) and declined with higher tumor burden.
- Safety: No grade ≥3 CRS; ICANS in 12.2% (≥grade 3: 2.2%); frequent taste changes (79%), skin events (69%), nail changes (56%), grade 3/4 neutropenia (62.2%), and infections (40%). Combination demonstrated superior efficacy and manageable toxicity in this high-burden, refractory MM population.
According to extended follow-up research presented by Saad Usmani, MD, Memorial Sloan Kettering Cancer Center, New York, New York, at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida, the combination of talquetamab (Tal) and teclistamab (Tec) delivers deep, durable responses for patients with triple-class exposed (TCE) relapsed/refractory (R/R) multiple myeloma (MM) and true extramedullary disease (EMD).
Researchers conducted the second phase of the RedirecTT-1 trial to determine the safety and efficacy of talquetamab combined with teclistamab among patients with EMD R/R MM. Patients treated with subcutaneous talquetamab (0.8 mg/kg) and teclistamab (3.0 mg/kg) every 2 weeks.
Overall, 90 patients were included in the analysis, and the median follow up was 16.2 months (range, 0.5 to 23.7). Most patients (82.2%) had soft tissue involvement, with 32.2% of them having organ EMD (most commonly liver) and 18.9% with nodal involvement. Approximately 39% of patients had non-secretory/oligo-secretory disease and 20% of patients had prior BCMA CAR-T exposure.
The overall response rate (ORR) was 77.8% (95% confidence interval [CI], 67.8 to 85.9), with 50.0% achieving complete response (CR) or better. The median duration of response [DOR] was not estimable, however, the 12-month DOR was 60.1%. The 12-month progression-free survival (PFS) rate was 55.6%. Additionally, the 12-month overall survival [OS] rate was 73.8%.
Response rates were stratified by baseline EMD tumor volume, which found patients with EMD tumor volume less than 25 cm² had an ORR of 90.7% (95% CI, 77.9 to 97.4; CR, ≥60.5%). Patients who had an EMD tumor volume between 25 to 50 cm² had an ORR of 66.7% (95% CI, 43.0 to 85.4; ≥CR 52.4%) and patients with an EMD tumor volume greater than 50 cm² had an ORR of 65.4% (95% CI, 44.3 to 82.8; ≥CR 30.8%).
In terms of safety, the combination was tolerable, with no grade ≥3 cytokine release syndrome (CRS) reported and only 12.2% experiencing immune effector cell-associated neurotoxicity syndrome, of which 2.2% of these were grade ≥3. The most common adverse events (AEs) were low-grade taste changes (79%), non-rash skin events (69%), and nail changes (56%). Grade 3/4 neutropenia occurred in 62.2% of patients, and 40% had grade 3 or 4 infections.
The researchers concluded, “With longer follow-up in pts with TCE RRMM with true EMD regardless of baseline tumor characteristics, Tal + Tec efficacy exceeded all approved therapies, including T-cell redirecting and cellular therapies, noting limitations of cross-study comparisons.”
They added, “These data continue to highlight the clinical benefit of the novel combination of Tal + Tec in pts with true EMD, a population with high disease burden and significant unmet need.”
Source:
Usmani S, Kumar S, Mateos MV, et al. Efficacy and safety of talquetamab + teclistamab in patients with Relapsed/Refractory multiple myeloma and extramedullary disease: Updated Phase 2 results from the redirectt-1 study with extended follow-up. Dec 6-9, 2025; Orlando, FL. Abstract: 698
