Infection Risk After LBCL CAR T-Cell Therapy: A Real-World Study Analysis Offers Clues

An analysis of a real-world study of patients with relapsed or refractory large B-cell lymphoma (LBCL) has assessed risk factors for, prevalence of, and outcomes from infection following receipt of CD19 chimeric antigen receptor (CAR) T-cell therapy. The authors published the analysis in Blood Advances.

First author for the analysis, Kitsada Wudhikarn, MD, from Chulalongkorn University in Bangkok, Thailand, wrote with colleagues that their findings “show a significant incidence of infection and IRM [infection-related mortality] in patients with R/R [relapsed or refractory] LBCL treated with CD19 CAR T-cell.”

The analysts also identified specific factors in patients linked to increased risk for infection following CD19 CAR T-cell therapy: having a history of infection prior to undergoing the treatment, Karnofsky score of 80 or less, cytokine release syndrome of grade 3 or worse severity, or immune effector cell-associated neurotoxicity syndrome of grade 3 or worse severity. Moreover, comparing axicabtagene ciloleucel and tisagenlecleucel CD19 CAR T-cell therapies in the patients, they found the former had a stronger association with infection risk.

The total study cohort was 3,350 patients with relapsed or refractory LBCL who had received commercial CD19 CAR T-cell therapy over a four-and-a-half-year period; the specific type received was axicabtagene ciloleucel in 2,804 patients and tisagenlecleucel in 546 patients.

The total cohort had a median follow-up of 24 months, following which 44% of the patients had died. In 12% of these patient deaths, infection was the primary cause of mortality, and the analysts calculated a 100-day IRM of 1.6%.

The analysts determined in the total cohort that having an infection within 100 days of receiving CD19 CAR T-cell therapy was independently associated with risk for worse overall survival after the 100^th day. In the cohort, infection within 100 days after receiving the treatment infusion occurred in 24.9% of patients. The analysts calculated a 100-day cumulative incidence of infection of 22% and an infection density of 0.43 per 100 patient-days.

Regarding specific types of infection in the cohort, bacterial infection occurred in 15.7% of patients and had a calculated infection density of 0.23 per 100 patient-days, viral infection in 11.2% of patients and had an infection density of 0.15 per 100 patient-days, and fungal infection in 3.2% of patients and had an infection density of 0.04 per 100 patient-days.

Dr. Wudhikarn and colleagues commented that their analysis findings “identify patients at heightened risk for infection, offering insights to guide potential interventions aimed at mitigating infection and improving patient outcomes after CAR T-cell therapy.”