Expert opinion on immunotherapy induced diabetes |
| |
| Institution: | 1. Department of endocrinology, l’institut du thorax, CHU Nantes, 44000 Nantes, France;2. Service d’endocrinologie, diabétologie, maladies métaboliques, CHU Dijon, hôpital François Mitterrand, 21034 Dijon cedex, France;3. Service de médecine interne B – Endocrinologie, 87042 Limoges cedex, France;1. Department of Thoracic/Head & Neck Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX;2. Department of Biostatistics, University of Texas MD Anderson Cancer Center, Houston, TX;3. Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX;4. Deparment of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, South Korea;5. College of Pharmacy, Seoul National University, Seoul, South Korea;1. Department of Cardiovascular Medicine, Flinders Medical Centre, Bedford Park, South Australia, Australia;2. Faculty of Medicine, Flinders University, Bedford Park, South Australia, Australia;1. Service d’endocrinologie, l''institut du thorax, CHU de Nantes, 44000 Nantes, France;2. Service d’endocrinologie, CHU de Angers, centre de référence de la thyroïde et des récepteurs hormonaux, 49933 Angers, France;3. Service d’endocrinologie et de maladies métaboliques, hôpital Huriez, 59037 Lille, France;4. Service d’endocrinologie, CHU de Rangueil-Larrey, 31059 Toulouse, France;2. Department of Anesthesiology, Texas Tech University Health Science Center, Lubbock, TX;3. St. Jude Children’s Hospital and Baptist Memorial Hospital, Memphis, TN;4. Division of Cardiothoracic Anesthesiology, Scott & White Memorial Hospital, The Texas A&M University Health Sciences Center College of Medicine, Temple, TX;5. Departments of Obstetrics & Gynecology and Internal Medicine, Academic Operations, Scott & White Healthcare, The Texas A&M University Health Sciences Center College of Medicine, Temple, TX;1. University of Maryland School of Public Health, College Park, MD, United States;2. National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States;3. Department of Epidemiology, Human Genetics & Environmental Sciences, University of Texas School of Public Health, Austin, TX, United States |
| |
| Abstract: | Immunotherapy often incurs side-effects, mainly involving the skin, digestive tract and endocrine system. The most frequent endocrine side-effects involve the pituitary and thyroid glands. Cases of insulin-dependent diabetes, whether autoimmune or not (type 1 or 1B) have been reported with PD-1/PD-L1 inhibitors, alone or in association with anti-CTLA-4 antibodies, and were systematically associated with sudden-onset insulinopenia, frequently leading to ketoacidosis or fulminant diabetes, requiring first-line insulin therapy. This adverse effect has not so far been reported with anti-CTLA-4 monotherapy.Recommendations- •R1. In patients receiving anti-PD-1 or anti-PD-L1 treatment, blood glucose should be assayed immediately in case of onset of polyuropolydipsic syndrome, weight loss or clinical signs of ketoacidosis, with HbA1c assay in case of pathologic findings. Anti-GAD antibodies should be screened for in first line, to establish the auto-immune origin of the diabetes; if absent, anti-IA2 and anti-ZnT8 antibodies may be screened for. Blood lipase should be assayed in clinical fulminant diabetes. Pancreatic imaging is not indicated at diagnosis.
- •R2. As anti-PD-1/PD-L1-induced diabetes may be fulminant, with severe insulinopenia, emergency first-line multi-injection insulin therapy should be initiated, with treatment and education in a specialized center or by a mobile diabetology team. The HbA1c target is < 8.0%. There are no other treatment options for immunotherapy-induced diabetes.
- •R3. Onset of diabetes under anti-PD-1 or anti-PD-L1 immunotherapy does not contraindicate continuation of treatment, although it may be interrupted for a few days in severe situations.
- •R4. Systematic fasting glucose and HbA1C assay is recommended ahead of any anti-PD-1 or anti-PD-L1 immunotherapy, to screen for pre-existing diabetes, defined by fasting glucose > 1.26 g/L, and/or glycemia > 2 g/L at any time of day in case of polyuria, and/or HbA1C ≥ 6.5%.
- •R5. Education should be ensured for patients undergoing anti-PD-1 or anti-PD-L1 immunotherapy, to recognize inaugural symptoms of diabetes (polyuropolydipsic syndrome, weight loss) or ketoacidosis (vomiting, digestive disorder).
- •R6. In patients undergoing anti-PD-1 or anti-PD-L1 immunotherapy, fasting glucose should be assayed at each course of treatment during the first 3 months, then every 3 months or urgently in case of onset of clinical signs.
- •R7. In case of diabetes pre-existing anti-PD-1 or anti-PD-L1 immunotherapy, glucose self-monitoring may be proposed or reinforced if already implemented.
- •R8. In view of the definitive nature of the induced diabetes, treatment and monitoring should be continued after the end of immunotherapy.
- •R9. Glucose monitoring is not recommended in anti-CTLA-4 therapy without associated anti-PD-1/PD-L1.
|
| |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ |
|
