Dual-Bispecific Approach Shows Strong Responses in EMD, Underscoring Need for Proactive Infection Management

In updated RedirecTT-1 (NCT04586426) data with nearly 17 months of follow-up, Saad Usmani, MD, MBA, FACP, FASCO, highlights how overall and complete response rates vary by extramedullary disease (EMD) tumor burden and what that means for selecting patients for talquetamab (Talvey; Johnson & Johnson)-teclistamab (Tecvayli; Johnson & Johnson) combination therapy.

Although lower-volume disease (<25 cm²) was associated with response rates above 90%, even patients with higher tumor burdens achieved meaningful benefit. At the same time, high rates of cytokine release syndrome (CRS), cytopenias, and serious infections emphasize the crucial role of vigilant monitoring and targeted prophylaxis, with pharmacists positioned to lead supportive care strategies such as intravenous immunoglobulin (IVIG) replacement and antimicrobial prevention.

Q: How do the updated overall response rates (ORR) and complete response (CR) rates across different extramedullary disease (EMD) tumor volumes influence your approach to identifying which patients might benefit most from talquetamab-teclistamab combination therapy?

Saad Usmani, MD, MBA, FACP, FASCO: Thank you so much for giving me the opportunity to share the results of the RedirecTT-1 study with an extended follow-up of almost around 17 months. This clinical trial was focused on the extramedullary disease patients who have a poor prognosis when given real-world standard of care treatments. So, this novel approach of giving a dual antigen-targeting bispecific strategy was shown to be highly effective. 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. So, compared to the standard of care treatments, I think we found this to be highly efficacious.

Of note, the patients who had a lower overall tumor burden, you know, less than 25 cm², had a very high response rate—over 90%. That doesn't mean that patients who had a higher disease burden, you know, 25 to 50 cm², or more than 50 cm², had responses around 67% and 65%, respectively. But it was the high-burden patients compared to the low-burden patients; the low-burden ones did have a higher response rate and CR rate.

Q: Given the high rates of cytokine release syndrome (CRS), cytopenias, and infection—particularly the 40% rate of grade 3/4 infections—what monitoring, prophylaxis, and supportive care strategies should pharmacists prioritize when managing patients receiving talquetamab-teclistamab?

Usmani: As you can see, the infections are primarily respiratory tract infections. So, provision of IVIG in patients who are hypogammaglobulinemic becomes a very important part. 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. On a case-to-case basis, one may even provide antibacterial prophylactic support to these patients.