PMID- 32973816 OWN - NLM STAT- MEDLINE DCOM- 20210520 LR - 20210520 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 11 DP - 2020 TI - Sintilimab-Induced Autoimmune Diabetes in a Patient With the Anti-tumor Effect of Partial Regression. PG - 2076 LID - 10.3389/fimmu.2020.02076 [doi] LID - 2076 AB - CONTEXT: Immune checkpoint blockades (ICBs) have been approved widely to treat various malignancies. Autoimmune diabetes mellitus, which can be caused by programmed cell death protein 1 (PD-1) inhibitors, is rare. Sintilimab, a monoclonal anti-PD-1 antibody, has been approved in China for the treatment of Hodgkin's lymphoma and was used in our clinical trial for patients with unresectable hepatocellular carcinoma (HCC). CASE PRESENTATION: We present the first case of autoimmune diabetes during Sintilimab treatment in a patient with unresectable HCC, accompanied by a remarkable anti-tumor effect of partial regression. A 56-year-old male with typical symptoms presented with diabetic ketoacidosis (DKA) at 24 weeks after Sintilimab initiation. His fasting plasma glucose level was 22.2 mmol/L, HbA1c was 7.8%, fasting insulin was 1.5 mIU/L, and fasting C-peptide was 1.12 ng/mL, which further decreased to 0.21 ng/mL 4 days later. The patient was diagnosed with new-onset diabetes mellitus using the oral glucose tolerance test. The anti-glutamic acid decarboxylase 65 antibody, anti-islet cell antibody, and anti-insulin antibody tests were all negative. For the type 1 diabetes-associated alleles of human leukocyte antigen (HLA) class I and II, the most relevant type was identified as HLA-A( *)0201. A diagnosis of PD-1 inhibitor-induced autoimmune diabetes was made. After rectification of DKA, he was treated with insulin therapy daily, which has since controlled his plasma glucose well. Thereafter, Sintilimab was been continued with sustained therapeutic effect. CONCLUSION: Due to unpredictability of this rare immune related adverse event (irAE), diabetes-related autoantibodies and C-peptide are recommended to be tested before immunotherapy, and plasma glucose monitoring should be performed. After plasma glucose is well controlled using insulin therapy, PD-1 inhibitor treatment might be continued, especially when the immunotherapy is effective. CI - Copyright (c) 2020 Wen, Zou, Chen, Bai and Liang. FAU - Wen, Liang AU - Wen L AD - Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. AD - Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China. AD - Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. AD - The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China. FAU - Zou, Xiuwen AU - Zou X AD - Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. AD - Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. AD - The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China. FAU - Chen, Yiwen AU - Chen Y AD - Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. AD - Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China. AD - Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. AD - The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China. FAU - Bai, Xueli AU - Bai X AD - Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. AD - Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China. AD - Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. AD - The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China. FAU - Liang, Tingbo AU - Liang T AD - Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. AD - Zhejiang Clinical Research Center of Hepatobiliary and Pancreatic Diseases, Hangzhou, China. AD - Zhejiang Provincial Key Laboratory of Pancreatic Disease, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China. AD - The Innovation Center for the Study of Pancreatic Diseases of Zhejiang Province, Hangzhou, China. LA - eng PT - Case Reports PT - Research Support, Non-U.S. Gov't DEP - 20200821 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antibodies, Monoclonal, Humanized) RN - 0 (Antineoplastic Agents, Immunological) RN - 0 (Autoantibodies) RN - 0 (Immune Checkpoint Inhibitors) RN - 0 (Insulin) RN - 0 (PDCD1 protein, human) RN - 0 (Programmed Cell Death 1 Receptor) RN - 8FU7FQ8UPK (sintilimab) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Antibodies, Monoclonal, Humanized/*adverse effects/therapeutic use MH - Antineoplastic Agents, Immunological/*adverse effects/therapeutic use MH - Autoantibodies/blood MH - Carcinoma, Hepatocellular/*drug therapy MH - China MH - Diabetes Mellitus, Type 1/*diagnosis/etiology MH - Glucose/metabolism MH - Humans MH - Immune Checkpoint Inhibitors/*adverse effects/therapeutic use MH - Immunotherapy/*methods MH - Insulin/administration & dosage MH - Liver Neoplasms/*drug therapy MH - Male MH - Middle Aged MH - Programmed Cell Death 1 Receptor/immunology PMC - PMC7472830 OTO - NOTNLM OT - PD-1 inhibitor OT - Sintilimab OT - autoimmune diabetes OT - hepatocellular carcinoma OT - immune related adverse event OT - plasma glucose EDAT- 2020/09/26 06:00 MHDA- 2021/05/21 06:00 PMCR- 2020/01/01 CRDT- 2020/09/25 06:02 PHST- 2020/04/01 00:00 [received] PHST- 2020/07/30 00:00 [accepted] PHST- 2020/09/25 06:02 [entrez] PHST- 2020/09/26 06:00 [pubmed] PHST- 2021/05/21 06:00 [medline] PHST- 2020/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2020.02076 [doi] PST - epublish SO - Front Immunol. 2020 Aug 21;11:2076. doi: 10.3389/fimmu.2020.02076. eCollection 2020.