Infectious complications of CD19-targeted chimeric antigen receptor-modified T-cell immunotherapy

Lymphodepletion chemotherapy with CD19-targeted chimeric antigen receptor–modified T (CAR-T)-cell immunotherapy is a novel treatment for refractory or relapsed B-cell malignancies. Infectious complications of this approach have not been systematically studied. We evaluated infections occurring between days 0 to 90 in 133 patients treated with CD19 CAR-T cells in a phase 1/2 study. We used Poisson and Cox regression to evaluate pre- and posttreatment risk factors for infection, respectively. The cohort included patients with acute lymphoblastic leukemia (ALL; n = 47), chronic lymphocytic leukemia (n = 24), and non-Hodgkin lymphoma (n = 62). There were 43 infections in 30 of 133 patients (23%) within 28 days after CAR–T-cell infusion with an infection density of 1.19 infections for every 100 days at risk. There was a lower infection density of 0.67 between days 29 and 90 (P = .02). The first infection occurred a median of 6 days after CAR–T-cell infusion. Six patients (5%) developed invasive fungal infections and 5 patients (4%) had life-threatening or fatal infections. Patients with ALL, ≥4 prior antitumor regimens, and receipt of the highest CAR–T-cell dose (2 x 107 cells per kg) had a higher infection density within 28 days in an adjusted model of baseline characteristics. Cytokine release syndrome (CRS) severity was the only factor after CAR–T-cell infusion associated with infection in a multivariable analysis. The incidence of infections wa...

Source: Blood - January 4, 2018 Category: Hematology Authors: Hill, J. A., Li, D., Hay, K. A., Green, M. L., Cherian, S., Chen, X., Riddell, S. R., Maloney, D. G., Boeckh, M., Turtle, C. J. Tags: Immunobiology and Immunotherapy, Free Research Articles, Clinical Trials and Observations Source Type: research