The RedirecTT-1 Phase 2 trial evaluated the efficacy and safety of talquetamab, an anti-GPRC5D×CD3 therapy, combined with teclistamab, an anti-BCMA×CD3 therapy, in patients with triple-class exposed relapsed/refractory multiple myeloma and true extramedullary disease. ​ With a median follow-up of 16.3 months, the combination therapy demonstrated an overall response rate of 77.8 percent, with 50 percent achieving complete response or better. ​ Lower extramedullary disease tumor volume under 25 cm² correlated with higher overall response rates of 90.7 percent. ​ The safety profile was consistent with each monotherapy, with common adverse events including cytokine release syndrome, neutropenia, taste changes, skin and nail-related events. ​ Grade 5 adverse events occurred in 12.2 percent of patients, with infections being the most common cause. ​ The findings highlight the clinical benefit of talquetamab and teclistamab in addressing the unmet needs of patients with high disease burden and poor outcomes. ​

Key Points:

• Research Focus: Talquetamab and teclistamab combination therapy for relapsed/refractory multiple myeloma with extramedullary disease. ​
• Patient Population: Triple-class exposed relapsed/refractory multiple myeloma with at least one nonradiated soft tissue plasmacytoma over 2 cm. ​
• Efficacy: Overall response rate of 77.8 percent, 50 percent achieving complete response or better. ​ Higher response rates observed in patients with lower tumor volume under 25 cm². ​
• Safety: Common adverse events include cytokine release syndrome, neutropenia, taste changes, skin and nail-related events, and infections. ​ Grade 5 adverse events occurred in 12.2 percent of patients, primarily due to infections. ​
• Conclusion: Talquetamab and teclistamab demonstrated superior efficacy compared to approved therapies for relapsed/refractory multiple myeloma with extramedullary disease, with a manageable safety profile. ​

Conclusion:
The RedirecTT-1 Phase 2 trial demonstrated that talquetamab and teclistamab is a promising combination therapy for patients with triple-class exposed relapsed/refractory multiple myeloma and true extramedullary disease, a population with poor outcomes and high disease burden. ​ The therapy achieved an overall response rate of 77.8 percent, with 50 percent of patients achieving complete response or better. ​ Lower extramedullary disease tumor volume under 25 cm² was associated with higher overall response rates of 90.7 percent. ​ The safety profile was consistent with each monotherapy, with common adverse events including cytokine release syndrome, neutropenia, taste changes, skin and nail-related events. ​ Grade 5 adverse events occurred in 12.2 percent of patients, primarily due to infections. ​ These findings underscore the clinical benefit of talquetamab and teclistamab in addressing the unmet needs of patients with relapsed/refractory multiple myeloma and extramedullary disease.

Authors: ​
Saad Usmani, Shaji Kumar, María-Victoria Mateos, J Christine Ye, Shebli Atrash, Hila Magen, Hang Quach, Michael Chu, Suzanne Trudel, Joshua Richter, Paula Rodriguez-Otero, Hun Chuah, Moshe Gatt, Eva Medvedova, Shahzad Raza, Dok Hyun Yoon, Tadao Ishida, Jeffrey Matous, Laura Rosiñol Dachs, Koichi Onodera, Carmela Maffucci, Emma Scott, Christoph Heuck, Jing Zhang, Todd Henninger, Lisa O'Rourke, Payal Thakkar, Mariacristina Festa, Lin Huang, Jiangxiu Zhou, Mikihiro Takamoto, Lixia Pei, Jiashen Lu, Nicholas Au, Maria Krevvata, Yaël Cohen ​