Dual Bispecific Antibody Combination Achieves 79% Response Rate in Relapsed/Refractory Multiple Myeloma with Extramedullary Disease
Key Insights
The combination of talquetamab and teclistamab achieved a 79% overall response rate with 53% complete response rate in patients with triple-class-exposed relapsed/refractory multiple myeloma and extramedullary disease.
Patients with lower tumor burden (<25 cm²) demonstrated superior response rates exceeding 90%, while those with higher disease burden still achieved meaningful responses of 65-67%.
The median progression-free survival reached 15.0 months with overall survival not yet reached, representing significant improvement over standard care for this poor-prognosis population.
The combination of talquetamab and teclistamab has demonstrated remarkable efficacy in patients with relapsed/refractory multiple myeloma and extramedullary disease, achieving a 79% overall response rate with extended follow-up of nearly 17 months in the phase 2 RedirecTT-1 trial. The dual bispecific antibody approach represents a significant advance for this challenging patient population, which typically has poor outcomes with standard treatments.
Strong Efficacy Across Disease Burden Levels
With a median follow-up of 16.8 months, the combination achieved an overall response rate of 79% (95% CI, 69%-87%) and a complete response or better rate of 53%. The median time to first response was 2.6 months, with a median time to best response of 5.1 months. Notably, the median duration of response was not reached, with a 12-month duration of response rate of 62.1%.
"The overall response rate with subsequent follow-up was almost 80%, the median progression-free survival is about 15 months at this time, and the overall survival has not been reached," said Saad Usmani, MD, MBA, FACP, FASCO, myeloma specialist at Memorial Sloan Kettering Cancer Center.
Response rates varied significantly by baseline extramedullary disease tumor volume. Patients with lower tumor burden (<25 cm²) achieved the highest response rates at 93% (95% CI, 81%-99%) with a complete response or better rate of 58%. Those with moderate tumor burden (25-50 cm²) had response rates of 67% (95% CI, 43%-95%) with 57% achieving complete response or better. Even patients with the highest tumor burden (>50 cm²) demonstrated meaningful benefit with 65% response rates and 42% complete response rates.
Survival Outcomes Show Promise
The median progression-free survival reached 15.0 months (95% CI, 10.3-not estimable), with a 12-month progression-free survival rate of 57.5%. The median overall survival was not reached, with a 12-month overall survival rate of 73.8% (95% CI, 63.3%-81.8%).
Both organ and non-organ extramedullary disease showed similar response patterns. Among patients with organ extramedullary disease (n=32), the overall response rate was 78% with a 56% complete response rate. For non-organ extramedullary disease patients (n=58), response rates were 79% with 52% achieving complete response or better.
Treatment Protocol and Patient Population
The study enrolled 90 patients who received subcutaneous talquetamab at 0.8 mg/kg every 2 weeks plus subcutaneous teclistamab at 3.0 mg/kg every 2 weeks. Patients could switch to monthly dosing after achieving very good partial response or better after 4 cycles, or after 6 cycles regardless of response.
Eligible patients had triple-class-exposed relapsed/refractory multiple myeloma with true extramedullary disease, defined as at least one nonradiated bone-independent soft tissue plasmacytoma of 2 cm or more. The median patient age was 64.5 years, with a median of 4 prior lines of treatment (range 1-10).
Safety Profile Requires Vigilant Management
The safety profile revealed significant toxicities requiring careful monitoring. The most common adverse events included oral toxicities (86.7% any grade, 4.4% grade 3/4), infections (80.0% any grade, 33.3% grade 3/4), cytokine release syndrome (77.8% any grade, 0% grade 3/4), and neutropenia (72.2% any grade, 63.3% grade 3/4).
Grade 3/4 infections occurred in 40% of patients, with the most common infections being upper respiratory tract infection (30.0%), COVID-19 (22.2%), pneumonia (21.1%), and urinary tract infection (13.3%). These infections were primarily respiratory tract infections and were mainly limited to the first 6 months of treatment.
Supportive Care Strategies
The high infection rates underscore the need for proactive management strategies. "Provision of IVIG in patients who are hypogammaglobulinemic becomes a very important part," Usmani noted. "We typically have varicella-zoster virus and pneumocystic jirovecii pneumonia prophylaxis for these patients and in patients who have had a prior history of bacterial pneumonias."
Treatment discontinuation due to adverse events occurred in 8.9% of patients, with 6 patients discontinuing both agents and 2 discontinuing only talquetamab. Grade 5 adverse events were reported in 12.2% of patients, with 6.7% being infection-related.
The frequency of new-onset adverse events decreased when patients switched from every-2-week to every-4-week dosing, with any-grade infections dropping from 72.2% to 60.7%, weight decrease from 51.1% to 26.8%, and oral adverse events from 85.6% to 21.4%.
Clinical Implications
The results represent a significant advance for patients with extramedullary multiple myeloma, a population with historically poor outcomes. "This clinical trial was focused on the extramedullary disease patients who have a poor prognosis when given real-world standard of care treatments," Usmani explained. "So, this novel approach of giving a dual antigen-targeting bispecific strategy was shown to be highly effective."
The findings, presented at the 2025 ASH Annual Meeting and published concurrently in the New England Journal of Medicine, establish the talquetamab-teclistamab combination as a promising treatment option for this challenging patient population, while highlighting the critical importance of comprehensive supportive care management.