title: Fulminant type I diabetes mellitus associated with nivolumab in a patient with relapsed classical Hodgkin lymphoma.
abstract: We report the case of a patient with relapsed classical Hodgkin lymphoma who developed fulminant type I diabetes mellitus as a severe adverse event of treatment with the anti-programmed cell death-1 (PD-1) antibody, nivolumab. On the first day of the sixth cycle, the blood glucose level was markedly elevated (375 mg/dL). Although neither ketoacidosis nor ketonuria was detected, the markedly acute onset of the hyperglycemia was consistent with the typical clinical course of fulminant type I diabetes mellitus, and this diagnosis was supported by clinical data. All autoantibodies associated with type I diabetes mellitus were negative. The endogenous insulin secretion ceased completely within 2 weeks. After the blood glucose level was brought under control, nivolumab was resumed and continued without other major adverse events. Human leukocyte antigen (HLA) analysis revealed that the patient carried the HLA-B*4002 haplotype, a susceptibility allele for this type of diabetes mellitus. This case suggests that fulminant type I diabetes mellitus may be triggered by nivolumab in patients with a genetic background associated with the condition, warranting careful future consideration of this particular adverse event.
authors.affiliation: Department of Hematology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. wmunakat@ncc.go.jp.
authors.forename: Wataru
authors.identifier: http://orcid.org/0000-0002-4679-0656
authors.initials: W
authors.lastname: Munakata
authors.affiliation: Department of General Internal Medicine, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Ken
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Department of Hematology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Yamauchi
authors.affiliation: Department of Hematology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Kensei
authors.initials: K
authors.lastname: Tobinai
mesh_terms: D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects* / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced* / Q000175:diagnosis / Q000235:genetics; D020022:Genetic Predisposition to Disease; D015235:HLA-B Antigens / Q000032:analysis / Q000235:genetics; D006689:Hodgkin Disease / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008297:Male; D000077594:Nivolumab; D012008:Recurrence
chemical_list: D000911:Antibodies, Monoclonal; D015235:HLA-B Antigens; D000077594:Nivolumab
keywords: Anti-PD-1 antibody; Fulminant type I diabetes mellitus; Immune-related adverse events; Nivolumab