Cemiplimab and diabetic ketoacidosis: a case report of a rare endocrinopathy associated with immune checkpoint inhibitors

BackgroundImmune checkpoint inhibitors (ICIs) have revolutionised the cancer treatment landscape in the last decades, improving the outcome of several tumours, such as cutaneous squamous cell carcinoma (cSCC). ICIs are antibodies blocking several immune checkpoint pathways, as cytotoxic T lymphocyte...

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Main Authors: Anna Arecco, Cristian Petolicchio, Alessandro Pastorino, Enrica Teresa Tanda, Lara Vera, Mara Boschetti, Francesco Cocchiara, Davide Carlo Maggi, Diego Ferone, Federico Gatto
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-03-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1550702/full
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author Anna Arecco
Cristian Petolicchio
Alessandro Pastorino
Enrica Teresa Tanda
Enrica Teresa Tanda
Lara Vera
Mara Boschetti
Mara Boschetti
Francesco Cocchiara
Davide Carlo Maggi
Davide Carlo Maggi
Diego Ferone
Diego Ferone
Federico Gatto
Federico Gatto
author_facet Anna Arecco
Cristian Petolicchio
Alessandro Pastorino
Enrica Teresa Tanda
Enrica Teresa Tanda
Lara Vera
Mara Boschetti
Mara Boschetti
Francesco Cocchiara
Davide Carlo Maggi
Davide Carlo Maggi
Diego Ferone
Diego Ferone
Federico Gatto
Federico Gatto
author_sort Anna Arecco
collection DOAJ
description BackgroundImmune checkpoint inhibitors (ICIs) have revolutionised the cancer treatment landscape in the last decades, improving the outcome of several tumours, such as cutaneous squamous cell carcinoma (cSCC). ICIs are antibodies blocking several immune checkpoint pathways, as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) with its ligand PD-L1. However, the activation of immune response can cause a broad range of side effects, called immune-related adverse events (irAEs). Endocrine irAEs are mainly represented by thyroid dysfunctions (thyrotoxicosis or hypothyroidism) and hypophysitis, while adrenal insufficiency and diabetes mellitus (DM) are less common. Diabetic ketoacidosis (DKA) is a potential life-threatening presentation of ICI-induced insulin-dependent DM (IDDM). This report presents a rare case of DKA and IDDM secondary to anti-PD-1 antibody cemiplimab therapy, and this is the third described in the literature to date.Case presentationWe describe the case of a 62-year-old female patient with metastatic perianal squamous cell carcinoma who developed DKA and IDDM after the fifth cycle of cemiplimab. Hyperglycemia (1187 mg/dL), metabolic acidosis (pH 7.27) with bicarbonate levels of 11.9 mmol/L, arterial partial pressure of carbon dioxide of 25.7 mmHg with increased anion gap (equal to 25), and hyperketonuria were present. Adequate glycaemic control was difficult to maintain, and intravenously therapy (insulin, sodium bicarbonate, potassium, and fluids) was required for a long time. Subcutaneous basal-bolus insulin treatment was started, but glycaemic control was scarce, also due to the concomitant administration of prednisone for immune-related hepatotoxicity, until the subject’s death.ConclusionThis report underlines the importance of the awareness on endocrine irAEs with ICIs, particularly life-threatening DKA. A baseline assessment of glycemia and glycated hemoglobin is mandatory, and we recommend a close monitoring of glycemic trend over time during ICIs therapy. Patients and their caregivers should be informed and counselled to recognise DKA signs and symptoms.
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spelling doaj-art-3dabfdad03794d298e37ac2ceca510c12025-08-20T03:40:40ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-03-011610.3389/fendo.2025.15507021550702Cemiplimab and diabetic ketoacidosis: a case report of a rare endocrinopathy associated with immune checkpoint inhibitorsAnna Arecco0Cristian Petolicchio1Alessandro Pastorino2Enrica Teresa Tanda3Enrica Teresa Tanda4Lara Vera5Mara Boschetti6Mara Boschetti7Francesco Cocchiara8Davide Carlo Maggi9Davide Carlo Maggi10Diego Ferone11Diego Ferone12Federico Gatto13Federico Gatto14Endocrinology Unit, Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genova, Genova, ItalyEndocrinology Unit, Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genova, Genova, ItalyMedical Oncology Unit 1, IRCCS Ospedale Policlinico San Martino, Genova, ItalyDepartment of Internal Medicine and Medical Specialties, University of Genova, Genova, ItalyMedical Oncology 2, IRCCS Policlinico San Martino, Genova, ItalyEndocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genova, ItalyEndocrinology Unit, Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genova, Genova, ItalyEndocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genova, ItalyEndocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genova, ItalyEndocrinology Unit, Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genova, Genova, ItalyEndocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genova, ItalyEndocrinology Unit, Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genova, Genova, ItalyEndocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genova, ItalyEndocrinology Unit, Department of Internal Medicine and Medical Specialties, School of Medical and Pharmaceutical Sciences, University of Genova, Genova, ItalyEndocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genova, ItalyBackgroundImmune checkpoint inhibitors (ICIs) have revolutionised the cancer treatment landscape in the last decades, improving the outcome of several tumours, such as cutaneous squamous cell carcinoma (cSCC). ICIs are antibodies blocking several immune checkpoint pathways, as cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) with its ligand PD-L1. However, the activation of immune response can cause a broad range of side effects, called immune-related adverse events (irAEs). Endocrine irAEs are mainly represented by thyroid dysfunctions (thyrotoxicosis or hypothyroidism) and hypophysitis, while adrenal insufficiency and diabetes mellitus (DM) are less common. Diabetic ketoacidosis (DKA) is a potential life-threatening presentation of ICI-induced insulin-dependent DM (IDDM). This report presents a rare case of DKA and IDDM secondary to anti-PD-1 antibody cemiplimab therapy, and this is the third described in the literature to date.Case presentationWe describe the case of a 62-year-old female patient with metastatic perianal squamous cell carcinoma who developed DKA and IDDM after the fifth cycle of cemiplimab. Hyperglycemia (1187 mg/dL), metabolic acidosis (pH 7.27) with bicarbonate levels of 11.9 mmol/L, arterial partial pressure of carbon dioxide of 25.7 mmHg with increased anion gap (equal to 25), and hyperketonuria were present. Adequate glycaemic control was difficult to maintain, and intravenously therapy (insulin, sodium bicarbonate, potassium, and fluids) was required for a long time. Subcutaneous basal-bolus insulin treatment was started, but glycaemic control was scarce, also due to the concomitant administration of prednisone for immune-related hepatotoxicity, until the subject’s death.ConclusionThis report underlines the importance of the awareness on endocrine irAEs with ICIs, particularly life-threatening DKA. A baseline assessment of glycemia and glycated hemoglobin is mandatory, and we recommend a close monitoring of glycemic trend over time during ICIs therapy. Patients and their caregivers should be informed and counselled to recognise DKA signs and symptoms.https://www.frontiersin.org/articles/10.3389/fendo.2025.1550702/fullimmune checkpoint inhibitorscemiplimabdiabetic ketoacidosisimmune-related adverse eventsdiabetes mellitusanti-PD-1 monoclonal antibody
spellingShingle Anna Arecco
Cristian Petolicchio
Alessandro Pastorino
Enrica Teresa Tanda
Enrica Teresa Tanda
Lara Vera
Mara Boschetti
Mara Boschetti
Francesco Cocchiara
Davide Carlo Maggi
Davide Carlo Maggi
Diego Ferone
Diego Ferone
Federico Gatto
Federico Gatto
Cemiplimab and diabetic ketoacidosis: a case report of a rare endocrinopathy associated with immune checkpoint inhibitors
Frontiers in Endocrinology
immune checkpoint inhibitors
cemiplimab
diabetic ketoacidosis
immune-related adverse events
diabetes mellitus
anti-PD-1 monoclonal antibody
title Cemiplimab and diabetic ketoacidosis: a case report of a rare endocrinopathy associated with immune checkpoint inhibitors
title_full Cemiplimab and diabetic ketoacidosis: a case report of a rare endocrinopathy associated with immune checkpoint inhibitors
title_fullStr Cemiplimab and diabetic ketoacidosis: a case report of a rare endocrinopathy associated with immune checkpoint inhibitors
title_full_unstemmed Cemiplimab and diabetic ketoacidosis: a case report of a rare endocrinopathy associated with immune checkpoint inhibitors
title_short Cemiplimab and diabetic ketoacidosis: a case report of a rare endocrinopathy associated with immune checkpoint inhibitors
title_sort cemiplimab and diabetic ketoacidosis a case report of a rare endocrinopathy associated with immune checkpoint inhibitors
topic immune checkpoint inhibitors
cemiplimab
diabetic ketoacidosis
immune-related adverse events
diabetes mellitus
anti-PD-1 monoclonal antibody
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1550702/full
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