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

Joshua A. Hill, Daniel Li, Kevin A. Hay, Margaret L. Green, Sindhu Cherian, Xueyan Chen, Stanley R. Riddell, David G. Maloney, Michael Boeckh and Cameron J. Turtle

Key Points

  • The incidence of infections after CD19 CAR–T-cell immunotherapy was similar to the incidence after other salvage chemoimmunotherapies.

  • Infections were more frequent in patients who had ALL, more prior antitumor treatment, a higher CAR–T-cell dose, or greater CRS severity.

Publisher's Note: There is a Blood Commentary on this article in this issue.

Abstract

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 × 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 was comparable to observations from clinical trials of salvage chemoimmunotherapies in similar patients. This trial was registered at www.clinicaltrials.gov as #NCT01865617.

  • Submitted July 13, 2017.
  • Accepted October 8, 2017.
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