Cytokine Release Syndrome Grade is a Predictive Marker for Infections in Relapsed or Refractory B-cell All Patients Treated with CAR T Cells.

Background: Chimeric antigen receptor (CAR)-modified T cells that target the CD19 antigen present a novel promising therapy for the treatment of relapsed B-cell acute lymphoblastic leukemia (ALL). Although cytokine release syndrome (CRS) and neurotoxicity have emerged as predominant non-infectious complications of CD19 CAR T cell therapy, infections associated with this treatment modality have not been well documented.

Methods: We analyzed infectious complications that followed CD19 CAR T cell therapy in 53 adult patients with relapsed ALL enrolled in a phase I clinical trial at Memorial Sloan Kettering Cancer Center (NCT01044069).

Results: Overall, 22 patients (42%) experienced 26 infections (17 bacterial, 4 fungal, 5 viral) within the first 30 days of CAR T cell infusion (CTI). Ten of 32 (31%) patients who achieved complete remission developed 15 infections between day+31 and day+180; the majority of these late infections were due to respiratory viruses. In general, bacterial, fungal, and viral infections were detected at a median of 18, 23, and 48 days, respectively, after CTI. Grade 3 or higher CRS was independently associated with increased risk of subsequent infection (adjusted hazard ratio (HR) 2.67, P=0.05) and in particular with bloodstream infection (adjusted HR 19.97, P=0.00). Three of 53 (6%) patients died due to infection-related cause.

Conclusions: Infections in adult patients with relapsed ALL following CD19 CAR T cell therapy are common. Understanding the infectious complications that are temporally coincident with CD19 CAR T cell therapy is critical for developing effective prophylactic and other supportive care measures to improve clinical outcomes.