A recent phase 2 clinical trial has revealed promising advancements in the treatment of relapsed/refractory large B-cell lymphoma (LBCL). The study, conducted by researchers at The University of Texas MD Anderson Cancer Center, evaluated the effectiveness of NKTR-255 when combined with CD19-directed CAR T-cell therapy. Notably, the research demonstrated a significant improvement in complete response (CR) rates at six months without substantially increasing toxicity. Specifically, patients receiving NKTR-255 showed higher CR rates compared to those on placebo, suggesting potential benefits for this challenging patient population.

Dr. Sairah Ahmed, an associate professor and director of the CAR T Program at MD Anderson Cancer Center, presented these findings at the 2025 Transplantation & Cellular Therapy Meetings. The randomized, double-blind, placebo-controlled trial involved three different dosing regimens of NKTR-255 or a placebo administered alongside standard CD19-directed CAR T-cell therapy. Historically, pivotal trials have reported six-month CR rates around 45%, but in this study, patients treated with NKTR-255 achieved a remarkable 73.5% CR rate, while those on placebo had only a 50% CR rate.

The study also focused on the safety profile of NKTR-255. While there was a slight increase in hematologic toxicity, the incidence of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) remained similar between the treatment and control groups. This indicates that NKTR-255 can enhance therapeutic outcomes without significantly worsening the side effects typically associated with CAR T-cell therapy.

These results underscore the potential of NKTR-255 to improve the efficacy of CAR T-cell therapy in treating relapsed/refractory LBCL. Dr. Ahmed emphasized the importance of further research to explore the long-term benefits and tolerability of NKTR-255. With its ability to boost CR rates while maintaining a manageable safety profile, NKTR-255 represents a promising addition to the arsenal of therapies available for patients with this aggressive form of lymphoma.