Cytokine release syndrome grade as a predictive marker for infections in patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with chimeric antigen receptor T cells Journal Article

   

Authors:	Park, J. H.; Romero, F. A.; Taur, Y.; Sadelain, M.; Brentjens, R. J.; Hohl, T. M.; Seo, S. K.
Article Title:	Cytokine release syndrome grade as a predictive marker for infections in patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with chimeric antigen receptor T cells
Abstract:	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 (B-ALL). Although cytokine release syndrome (CRS) and neurotoxicity have emerged as predominant noninfectious 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 B-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, and 5 viral) within the first 30 days of CAR T-cell infusion. In 10 of 32 (31%) patients in whom complete remission was achieved, 15 infections developed between days 31 and 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 CAR T-cell infusion. CRS grade 3 or higher was independently associated with increased risk of subsequent infection (adjusted hazard ratio [HR], 2.67; P =.05) and in particular with bloodstream infection (adjusted HR, 19.97; P < .001). Three of 53 patients (6%) died of an infection-related cause. Conclusions. Infections in adult patients with relapsed B-ALL are common after CD19 CAR T-cell therapy. 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.
Keywords:	complications; management; therapy; adults; malignancies; cytokine release syndrome; hematologic; clinical-practice guidelines; america; lymphoblastic leukemia; car t-cell therapy; relapsed acute; early infections; late infections; diseases-society; 2010 update; thoracic-society
Journal Title:	Clinical Infectious Diseases
Volume:	67
Issue:	4
ISSN:	1058-4838
Publisher:	Oxford University Press
Date Published:	2018-08-15
Start Page:	533
End Page:	540
Language:	English
ACCESSION:	WOS:000441000000013
DOI:	10.1093/cid/ciy152
PROVIDER:	wos
PMCID:	PMC6070095
PUBMED:	29481659
Notes:	Article -- Source: Wos