Dr Ahmed on NKTR-255 With CD19-Directed CAR T-Cell Therapy in R/R LBCL

"The main takeaway from this particular studystudy was that NKTR-255 improves the CR rate at six months without increasing the toxicity profile in terms of CRS and ICANS. [This agent] does have slightly more hematologic toxicity but otherwise is very well tolerated.”

Sairah Ahmed, MD, associate professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, and director, of the CAR T Program, The University of Texas MD Anderson Cancer Center, discusses evaluating NKTR-255 in combination with CD19-directed CAR T-cell therapy in patients with relapsed/refractory large B-cell lymphoma (LBCL).

Ahmed and colleagues presented findings from a phase 2 trial (NCT05664217) at the 2025 Transplantation & Cellular Therapy Meetings.

The randomized, double-blind, placebo-controlled, double-blinded study assessed the effect of NKTR-255’s impact on complete response (CR) rates at six months following commercial CD19-directed CAR T-cell therapy. Patients were assigned to one of three NKTR-255 dosing regimens or placebo.

Results demonstrated that 73% of patients in the combined NKTR-255 cohorts achieved a CR at six months compared with 50% of those in the placebo arm. Historically, pivotal trials of CD19-directed CAR T-cell therapy have reported six-month CR rates of approximately 45%, underscoring the potential benefit of NKTR-255 in this setting.

Ahemd explains that the rate of adverse effects associated with CAR T-cell therapy, particularly cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), did not differ significantly between groups. While Although NKTR-255 was linked to a slight increase in hematologic toxicity, the agent was otherwise well tolerated.

Ahmed concludes that these findings highlight the potential role of NKTR-255 in improving CAR T-cell therapy outcomes without exacerbating treatment-related toxicities. Given the observed improvement in CR rates and the manageable safety profile, Ahmed explains that further investigation is warranted to determine the long-term impact effect of NKTR-255 on disease progression, survival outcomes, and overall treatment tolerability in patients with relapsed/refractory LBCL.