Dr Ahmed on Challenges Treating Patients With R/R LBCL Following Exposure to CAR T-Cell Therapy

"There are multiple challenges for patients who are receiving CAR T-cell therapy, but the one that is front and center is that the majority of patients do not experience durable responses, so they go through a very complicated procedure with toxicity that is unique…[and experience] financial toxicity without long-term remission. Ultimately, that’s what we would like to improve."

Sairah Ahmed, MD, an associate professor in the Department of Lymphoma/Myeloma in the Division of Cancer Medicine and director of the CAR T Program at The University of Texas MD Anderson Cancer Center, discusses current challenges that arise when treating patients with large B-cell lymphoma (LBCL) who previously received CAR T-cell therapy.

A major challenge associated with CAR T-cell therapy for relapsed/refractory LBCL is that a substantial portion of patients do not achieve long-term remission, despite undergoing a complex and toxic procedure that includes unique adverse effects, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, Ahmed begins. Approximately 40% of patients achieve long-term remission, but 60% either do not respond or relapse after treatment, according to Ahmed. This creates significant emotional, physical, and financial burdens for both patients and their caregivers, who may be unable to work during the intensive treatment period, Ahmed explains. Therefore, efforts are ongoing to improve the durability of response with CAR T-cell therapy for these patients, Ahmed notes.

One such attempt was a phase 2 trial (NCT05664217) evaluating whether the addition of the interleukin-15 agonist NKTR-255 to CD19-directed CAR T-cell therapy could improve CAR T-cell fitness in patients with relapsed/refractory LBCL. Results presented at the 2025 Transplantation & Cellular Therapy Meetings showed that 73% of patients in the combined NKTR-255 cohort (n = 11) achieved a complete remission (CR) at 6 months compared with 50% of those in the placebo group (n = 4). Historically, pivotal trials of CD19-directed CAR T-cell therapy have reported 6-month CR rates of approximately 45%, highlighting the potential benefit of incorporating NKTR-255 to improve outcomes in this patient population, Ahmed concludes.

Disclosures: Ahmed has received institutional support for clinical trials from Caribou, Chimagen, Genmab, Janssen, KITE/Gilead, Merck, Nektar, and Xencor; is a member of the Chimagen scientific advisory committee; serves on the Data Safety Monitoring Board for Myeloid Therapeutics; and serves as a consultant for ADC Therapeutics, Bristol Myers Squibb, and KITE/Gilead Sciences.