Nivolumab-induced diabetes mellitus—a case report with literature review of the treatment options
BackgroundImmune checkpoint inhibitor (ICI) treatment has become important for treating various cancer types, including metastatic renal cell carcinoma. However, ICI treatment can lead to endocrine immune-related adverse events (irAEs) by overstimulating the patient’s immune system. Here, we report...
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| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1248919/full |
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| author | Eveline Daetwyler Alfred Zippelius Alfred Zippelius Simona Danioth Marc Y. Donath Marc Y. Donath Lara Gut Lara Gut |
| author_facet | Eveline Daetwyler Alfred Zippelius Alfred Zippelius Simona Danioth Marc Y. Donath Marc Y. Donath Lara Gut Lara Gut |
| author_sort | Eveline Daetwyler |
| collection | DOAJ |
| description | BackgroundImmune checkpoint inhibitor (ICI) treatment has become important for treating various cancer types, including metastatic renal cell carcinoma. However, ICI treatment can lead to endocrine immune-related adverse events (irAEs) by overstimulating the patient’s immune system. Here, we report a rare case of a new onset of diabetes mellitus (DM), caused by nivolumab, and we discuss the feasible treatment options with a focus on TNF antagonism.Case presentationA 50-year-old man was diagnosed with metastatic renal cell carcinoma. Due to systemic progression, a combined immunotherapy with ipilimumab and nivolumab was initiated, according to the current study protocol (SAKK 07/17). The administration of ipilimumab was stopped after 10 months, due to partial response as seen in the computer tomography (CT), and nivolumab was continued as monotherapy. Fourteen months after the start of the treatment, the patient was admitted to the emergency department with lethargy, vomiting, blurred vision, polydipsia, and polyuria. The diagnosis of DM with diabetic ketoacidosis was established, although autoantibodies to β-cells were not detectable. Intravenous fluids and insulin infusion treatment were immediately initiated with switching to a subcutaneous administration after 1 day. In addition, the patient received an infusion of the TNF inhibitor infliximab 4 days and 2 weeks after the initial diagnosis of DM. However, the C-peptide values remained low, indicating a sustained insulin deficiency, and the patient remained on basal bolus insulin treatment. Two months later, nivolumab treatment was restarted without destabilization of the diabetic situation.ConclusionsIn contrast to the treatment of other irAEs, the administration of corticosteroids is not recommended in ICI-induced DM. The options for further treatment are mainly based on the low numbers of case series and case reports. In our case, the administration of infliximab—in an attempt to salvage the function of β-cells—was not successful, and this is in contrast to some previous reports. This apparent discrepancy may be explained by the absence of insulin resistance in our case. There is so far no evidence for immunosuppressive treatment in this situation. Prompt recognition and immediate start of insulin treatment are most important in its management. |
| first_indexed | 2024-03-11T15:34:02Z |
| format | Article |
| id | doaj.art-5533861235464a58bc0518814c1bcc62 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T15:34:02Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-5533861235464a58bc0518814c1bcc622023-10-26T23:43:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12489191248919Nivolumab-induced diabetes mellitus—a case report with literature review of the treatment optionsEveline Daetwyler0Alfred Zippelius1Alfred Zippelius2Simona Danioth3Marc Y. Donath4Marc Y. Donath5Lara Gut6Lara Gut7Department of Medical Oncology, University Hospital Basel, Basel, SwitzerlandDepartment of Medical Oncology, University Hospital Basel, Basel, SwitzerlandDepartment of Biomedicine, University of Basel, Basel, SwitzerlandClinic for Endocrinology, Diabetes & Metabolism, Luzern Cantonal Hospital, Luzern, SwitzerlandDepartment of Biomedicine, University of Basel, Basel, SwitzerlandClinic for Endocrinology, Diabetes & Metabolism, University Hospital Basel, Basel, SwitzerlandClinic for Endocrinology, Diabetes & Metabolism, University Hospital Basel, Basel, SwitzerlandClinic for Endocrinology & Diabetes, Medical University Clinic Baselland, Liestal, SwitzerlandBackgroundImmune checkpoint inhibitor (ICI) treatment has become important for treating various cancer types, including metastatic renal cell carcinoma. However, ICI treatment can lead to endocrine immune-related adverse events (irAEs) by overstimulating the patient’s immune system. Here, we report a rare case of a new onset of diabetes mellitus (DM), caused by nivolumab, and we discuss the feasible treatment options with a focus on TNF antagonism.Case presentationA 50-year-old man was diagnosed with metastatic renal cell carcinoma. Due to systemic progression, a combined immunotherapy with ipilimumab and nivolumab was initiated, according to the current study protocol (SAKK 07/17). The administration of ipilimumab was stopped after 10 months, due to partial response as seen in the computer tomography (CT), and nivolumab was continued as monotherapy. Fourteen months after the start of the treatment, the patient was admitted to the emergency department with lethargy, vomiting, blurred vision, polydipsia, and polyuria. The diagnosis of DM with diabetic ketoacidosis was established, although autoantibodies to β-cells were not detectable. Intravenous fluids and insulin infusion treatment were immediately initiated with switching to a subcutaneous administration after 1 day. In addition, the patient received an infusion of the TNF inhibitor infliximab 4 days and 2 weeks after the initial diagnosis of DM. However, the C-peptide values remained low, indicating a sustained insulin deficiency, and the patient remained on basal bolus insulin treatment. Two months later, nivolumab treatment was restarted without destabilization of the diabetic situation.ConclusionsIn contrast to the treatment of other irAEs, the administration of corticosteroids is not recommended in ICI-induced DM. The options for further treatment are mainly based on the low numbers of case series and case reports. In our case, the administration of infliximab—in an attempt to salvage the function of β-cells—was not successful, and this is in contrast to some previous reports. This apparent discrepancy may be explained by the absence of insulin resistance in our case. There is so far no evidence for immunosuppressive treatment in this situation. Prompt recognition and immediate start of insulin treatment are most important in its management.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1248919/fullimmune checkpoint inhibitor (ICI)immune-related adverse event (irAE)diabetes mellitusTNF blockadecase report |
| spellingShingle | Eveline Daetwyler Alfred Zippelius Alfred Zippelius Simona Danioth Marc Y. Donath Marc Y. Donath Lara Gut Lara Gut Nivolumab-induced diabetes mellitus—a case report with literature review of the treatment options Frontiers in Immunology immune checkpoint inhibitor (ICI) immune-related adverse event (irAE) diabetes mellitus TNF blockade case report |
| title | Nivolumab-induced diabetes mellitus—a case report with literature review of the treatment options |
| title_full | Nivolumab-induced diabetes mellitus—a case report with literature review of the treatment options |
| title_fullStr | Nivolumab-induced diabetes mellitus—a case report with literature review of the treatment options |
| title_full_unstemmed | Nivolumab-induced diabetes mellitus—a case report with literature review of the treatment options |
| title_short | Nivolumab-induced diabetes mellitus—a case report with literature review of the treatment options |
| title_sort | nivolumab induced diabetes mellitus a case report with literature review of the treatment options |
| topic | immune checkpoint inhibitor (ICI) immune-related adverse event (irAE) diabetes mellitus TNF blockade case report |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1248919/full |
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