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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