title: Current concepts in the diagnosis and management of cytokine release syndrome.
abstract: As immune-based therapies for cancer become potent, more effective, and more widely available, optimal management of their unique toxicities becomes increasingly important. Cytokine release syndrome (CRS) is a potentially life-threatening toxicity that has been observed following administration of natural and bispecific antibodies and, more recently, following adoptive T-cell therapies for cancer. CRS is associated with elevated circulating levels of several cytokines including interleukin (IL)-6 and interferon γ, and uncontrolled studies demonstrate that immunosuppression using tocilizumab, an anti-IL-6 receptor antibody, with or without corticosteroids, can reverse the syndrome. However, because early and aggressive immunosuppression could limit the efficacy of the immunotherapy, current approaches seek to limit administration of immunosuppressive therapy to patients at risk for life-threatening consequences of the syndrome. This report presents a novel system to grade the severity of CRS in individual patients and a treatment algorithm for management of CRS based on severity. The goal of our approach is to maximize the chance for therapeutic benefit from the immunotherapy while minimizing the risk for life threatening complications of CRS.
authors.affiliation: Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD;
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Lee
authors.affiliation: Seattle Children's Hospital, Seattle, WA;
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gardner
authors.affiliation: Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, PA;
authors.forename: David L
authors.initials: DL
authors.lastname: Porter
authors.affiliation: Texas Children's Hospital, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX; and.
authors.forename: Chrystal U
authors.initials: CU
authors.lastname: Louis
authors.affiliation: Texas Children's Hospital, Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, TX; and.
authors.forename: Nabil
authors.initials: N
authors.lastname: Ahmed
authors.affiliation: Seattle Children's Hospital, Seattle, WA;
authors.forename: Michael
authors.initials: M
authors.lastname: Jensen
authors.affiliation: Division of Hematology-Oncology, University of Pennsylvania, Philadelphia, PA; Children's Hospital of Philadelphia Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Grupp
authors.affiliation: Pediatric Oncology Branch, National Cancer Institute, Bethesda, MD;
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Mackall
mesh_terms: D002648:Child; D016207:Cytokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007154:Immune System Diseases / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*; D007938:Leukemia / Q000175:diagnosis / Q000276:immunology / Q000378:metabolism* / Q000628:therapy; D010257:Paraneoplastic Syndromes / Q000175:diagnosis* / Q000378:metabolism / Q000628:therapy*; D055815:Young Adult
chemical_list: D016207:Cytokines