Rituximab induced cytokine release with high serum IP-10 (CXCL10) concentrations is associated with infusion reactions.

Autor: Moore JE; James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, United States; Department of Pharmacy, University of Rochester Medical Center, Rochester, NY, United States., Bloom PC; James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, United States., Chu CC; James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, United States; Division of Hematology/Oncology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, United States., Bruno JE; Center for Vaccine Biology & Immunology, University of Rochester Medical Center, Rochester, NY, United States; Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, United States., Herne CA; James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, United States., Baran AM; Department of Biostatistics and Computational Biology, University of Rochester Medical Center, Rochester, NY, United States., Quataert SA; Center for Vaccine Biology & Immunology, University of Rochester Medical Center, Rochester, NY, United States; Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, United States., Mosmann TR; Center for Vaccine Biology & Immunology, University of Rochester Medical Center, Rochester, NY, United States; Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY, United States., Taylor RP; Department of Biochemistry and Molecular Genetics, University of Virginia School of Medicine, Charlottesville, VA, United States., Wallace DS; James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, United States; Division of Hematology/Oncology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, United States., Elliott MR; Center for Cell Clearance and the Department of Microbiology, Immunology, and Cancer Biology, University of Virginia, Charlottesville, VA, United States., Barr PM; James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, United States; Division of Hematology/Oncology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, United States., Zent CS; James P. Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, United States; Division of Hematology/Oncology, Department of Medicine, University of Rochester Medical Center, Rochester, NY, United States. Electronic address: clive_zent@urmc.rochester.edu.
Jazyk: angličtina
Zdroj: Leukemia research [Leuk Res] 2023 Jun; Vol. 129, pp. 107072. Date of Electronic Publication: 2023 Mar 29.
DOI: 10.1016/j.leukres.2023.107072
Abstrakt: Monoclonal antibody induced infusion reactions (IRs) can be serious and even fatal. We used clinical data and blood samples from 37 treatment naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) initiating therapy for progressive disease with a single 50 mg dose of intravenous (IV) rituximab at 25 mg/h. Twenty-four (65 %) patients had IRs at a median of 78 min (range 35-128) and rituximab dose of 32 mg (range 15-50). IR risk did not correlate with patient or CLL characteristics, CLL counts or CD20 levels, or serum rituximab or complement concentrations. Thirty-five (95 %) patients had cytokine release response with a ≥ 4-fold increase in serum concentration of ≥ 1 inflammatory cytokine. IRs were associated with significantly higher post-infusion serum concentrations of gamma interferon induced cytokines IP-10, IL-6 and IL-8. IP-10 concentrations increased ≥ 4-fold in all patients with an IR and were above the upper limit of detection (40,000 pg/ml) in 17 (71 %). In contrast, to only three (23 %) patients without an IR had an ≥ 4-fold increase in serum concentrations of IP-10 (highest 22,013 pg/ml). Our data suggest that cytokine release could be initiated by activation of effector cells responsible for clearance of circulating CLL cells with IRs occurring in those with higher levels of gamma interferon induced cytokines. These novel insights could inform future research to better understand and manage IRs and understand the role of cytokines in the control of cytotoxic immune responses to mAb.
Competing Interests: Declaration of Competing Interest PBM and CSZ report funding for research through the University of Rochester from AstraZeneca and TG Therapeutics, CSZ reports funding for research through the University of Rochester from GenMab, and PMB reports serving as a consultant for Pharmacyclics, AbbVie, Genentech and Seattle Genetics. The other authors report no potential conflicts of interests.
(Copyright © 2023 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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