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
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MSK Authors
  1. Renier J Brentjens
    237 Brentjens
  2. Susan Seo
    74 Seo
  3. Tobias Martin Hohl
    59 Hohl
  4. Jae Hong Park
    182 Park
  5. Michel W J Sadelain
    491 Sadelain
  6. Ying Taur
    101 Taur
  7. Fabian Andres Romero
    5 Romero