BACKGROUND The use of immune checkpoint inhibitor (ICI) therapy is becoming a standard of care for several cancers. Monoclonal antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) or its ligand (PD-L1) cause a broad spectrum of autoimmune adverse events. ICI-induced type 1 diabetes mellitus (T1DM) is extremely rare (< 1%) but potentially life-threatening. It appears to be more common with PD-1 blockade (or combination immunotherapy) than with anti-CTLA-4 therapy, often during the first three to six months of therapy. CASES PRESENTATION We report an acute onset T1DM with severe inaugural diabetic ketoacidosis (DKA) and remarkably elevated Glutamic Acid Decarboxylase antibody (GADA) titres following a single administration of combined ICI therapy with nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4) in two adult patients with advanced metastatic melanoma. In these cases, the time to diabetes onset was remarkably short (two and five weeks), and one presented with fulminous T1DM in a previous long-standing type 2 diabetes mellitus. CONCLUSIONS Oncological patients treated with combination therapy of anti-PD-1 and anti-CTLA-4 can develop a particular pattern of T1DM, with very rapid onset within a few weeks after starting ICI therapy, even in the presence of an existing type 2 diabetes. ICI-induced T1DM is a medical emergency in presence of severe inaugural DKA and requires a collaboration between specialists and primary care physicians, as well as patient education, for early diagnosis and supportive care.

中文翻译：

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免疫检查点抑制剂联合纳武单抗和伊匹单抗治疗单次给药后导致急性发作 1 型糖尿病：两例病例报告。

背景技术免疫检查点抑制剂（ICI）疗法的使用正在成为多种癌症的护理标准。靶向细胞毒性 T 淋巴细胞抗原 4 (CTLA-4) 和程序性细胞死亡蛋白 1 (PD-1) 或其配体 (PD-L1) 的单克隆抗体会导致广泛的自身免疫不良事件。ICI 诱发的 1 型糖尿病 (T1DM) 极为罕见 (< 1%)，但可能危及生命。PD-1 阻断（或联合免疫疗法）似乎比抗 CTLA-4 疗法更常见，通常发生在治疗的前三到六个月内。病例介绍 我们报告了一名急性发作的 T1DM，在单次给予纳武单抗（抗 PD-1）和易普利姆玛（抗 CTLA）联合 ICI 治疗后，伴有严重的首次糖尿病酮症酸中毒 (DKA) 和谷氨酸脱羧酶抗体 (GADA) 滴度显着升高-4) 两名患有晚期转移性黑色素瘤的成年患者。在这些病例中，糖尿病发病时间非常短（两周和五周），其中一人在既往长期患有 2 型糖尿病的情况下出现暴发性 T1DM。结论：接受抗 PD-1 和抗 CTLA-4 联合治疗的肿瘤患者可能会出现一种特殊的 T1DM 模式，即使在患有 2 型糖尿病的情况下，在开始 ICI 治疗后几周内也会非常迅速地发病。ICI 诱发的 T1DM 是严重首次 DKA 的医疗紧急情况，需要专家和初级保健医生之间的合作以及患者教育，以进行早期诊断和支持治疗。