Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy.

TitleCytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy.
Publication TypeJournal Article
Year of Publication2013
AuthorsTeachey DT, Rheingold SR, Maude SL, Zugmaier G, Barrett DM, Seif AE, Nichols KE, Suppa EK, Kalos M, Berg RA, Fitzgerald JC, Aplenc R, Gore L, Grupp SA
JournalBlood
Volume121
Issue26
Pagination5154-7
Date Published2013 Jun 27
ISSN1528-0020
KeywordsAntibodies, Bispecific, Antibodies, Monoclonal, Humanized, Child, Cytokines, Down Syndrome, Follow-Up Studies, Humans, Immune System Diseases, Immunotherapy, Lymphohistiocytosis, Hemophagocytic, Macrophage Activation, Male, Precursor B-Cell Lymphoblastic Leukemia-Lymphoma, Prospective Studies, Receptors, Interleukin-6, Syndrome, T-Lymphocytes, Cytotoxic, Treatment Outcome
Abstract

Blinatumomab is a CD19/CD3-bispecific T-cell receptor-engaging (BiTE) antibody with efficacy in refractory B-precursor acute lymphoblastic leukemia. Some patients treated with blinatumomab and other T cell-activating therapies develop cytokine release syndrome (CRS). We hypothesized that patients with more severe toxicity may experience abnormal macrophage activation triggered by the release of cytokines by T-cell receptor-activated cytotoxic T cells engaged by BiTE antibodies and leading to hemophagocytic lymphohistiocytosis (HLH). We prospectively monitored a patient during blinatumomab treatment and observed that he developed HLH. He became ill 36 hours into the infusion with fever, respiratory failure, and circulatory collapse. He developed hyperferritinemia, cytopenias, hypofibrinogenemia, and a cytokine profile diagnostic for HLH. The HLH continued to progress after discontinuation of blinatumomab; however, he had rapid improvement after IL-6 receptor-directed therapy with tocilizumab. Patients treated with T cell-activating therapies, including blinatumomab, should be monitored for HLH, and cytokine-directed therapy may be considered in cases of life-threatening CRS. This trial was registered at www.clinicaltrials.gov as #NCT00103285.

DOI10.1182/blood-2013-02-485623
Alternate JournalBlood
PubMed ID23678006
PubMed Central IDPMC4123427
Grant ListP30 CA016520 / CA / NCI NIH HHS / United States
R01 CA102646 / CA / NCI NIH HHS / United States
R01 CA116660 / CA / NCI NIH HHS / United States
T32 CA009615 / CA / NCI NIH HHS / United States