Expert opinion on immunotherapy induced diabetes - 18/10/18
, Perrine Buffier b, Benjamin Bouillet b, Françoise Archambeaud c, Bruno Vergès b, Bertrand Cariou a
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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>1.26g/L, and/or glycemia>2g/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. |
Plan
Vol 79 - N° 5
P. 545-549 - octobre 2018 Retour au numéro
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