Fulminant type 1 diabetes mellitus with anti‐programmed cell death‐1 therapy

Okamoto, Motozumi; Okamoto, Mitsuhiro; Gotoh, Koro; Masaki, Takayuki; Ozeki, Yoshinori; Ando, Hisae; Anai, Manabu; Sato, Ayumu; Yoshida, Yuichi; Ueda, Satoshi; Kakuma, Tatsuyuki; Shibata, Hirotaka

doi:10.1111/jdi.12531

Cited by 144 publications

(110 citation statements)

References 10 publications

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“…In the study of lambrolizumab, hyperglycemic events were not reported [37]; however, in patients treated with pembrolizumab after approval, hyperglycemic events were reported in 45% to 49% of patients, and 3% to 6% experienced grade 3 or 4 hyperglycemic events. Among 2,117 patients, fulminant type 1 diabetes mellitus (T1DM) occurred with an incidence rate of 0.1% and at various stages of treatment, ranging from 1 week to 12 months [4142]. …”

Section: Immunotherapy: Checkpoint Inhibitorsmentioning

confidence: 99%

Acute Hyperglycemia Associated with Anti-Cancer Medication

Hwangbo

Lee

2017

Endocrinol Metab

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Hyperglycemia during chemotherapy occurs in approximately 10% to 30% of patients. Glucocorticoids and L-asparaginase are well known to cause acute hyperglycemia during chemotherapy. Long-term hyperglycemia is also frequently observed, especially in patients with hematologic malignancies treated with L-asparaginase-based regimens and total body irradiation. Glucocorticoid-induced hyperglycemia often develops because of increased insulin resistance, diminished insulin secretion, and exaggerated hepatic glucose output. Screening strategies for this condition include random glucose testing, hemoglobin A1c testing, oral glucose loading, and fasting plasma glucose screens. The management of hyperglycemia starts with insulin or sulfonylurea, depending on the type, dose, and delivery of the glucocorticoid formulation. Mammalian target of rapamycin (mTOR) inhibitors are associated with a high incidence of hyperglycemia, ranging from 13% to 50%. Immunotherapy, such as anti-programmed death 1 (PD-1) antibody treatment, induces hyperglycemia with a prevalence of 0.1%. The proposed mechanism of immunotherapy-induced hyperglycemia is an autoimmune process (insulitis). Withdrawal of the PD-1 inhibitor is the primary treatment for severe hyperglycemia. The efficacy of glucocorticoid therapy is not fully established and the decision to resume PD-1 inhibitor therapy depends on the severity of the hyperglycemia. Diabetic patients should achieve optimized glycemic control before initiating treatment, and glucose levels should be monitored periodically in patients initiating mTOR inhibitor or PD-1 inhibitor therapy. With regard to hyperglycemia caused by anti-cancer therapy, frequent monitoring and proper management are important for promoting the efficacy of anti-cancer therapy and improving patients' quality of life.

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Section: Immunotherapy: Checkpoint Inhibitorsmentioning

confidence: 99%

Acute Hyperglycemia Associated with Anti-Cancer Medication

Hwangbo

Lee

2017

Endocrinol Metab

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“…Only few cases of immunotherapy related fulminant diabetes mellitus have been reported so far. [3–5]…”

Section: Introductionmentioning

confidence: 99%

Combined checkpoint inhibitor therapy causing diabetic ketoacidosis in metastatic melanoma

Changizzadeh¹,

Mukkamalla²,

Armenio³

2017

j. immunotherapy cancer

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BackgroundThere has been a significant improvement in survival of advanced malignancies with the advent of checkpoint inhibitors. These newer treatment modalities come with a wide spectrum of unique side effects, termed immune related adverse events (irAE), ranging from mild skin rash to severe colitis. Included in that spectrum is the rare side effect of autoimmune diabetes mellitus. Despite a few case reports illustrating the incidence of autoimmune diabetes associated with immunotherapy, there has not been much mentioned about exacerbation or acceleration of hyperglycemia in non-autoimmune settings leading to de novo diagnosis of type 2 diabetes mellitus.Case presentationWe report the case of a 42 year old man with metastatic melanoma and no prior history of diabetes mellitus, who presented with diabetic ketoacidosis (DKA) after 3 cycles of combination checkpoint inhibitor therapy using nivolumab and ipilimumab. New onset diabetes mellitus was diagnosed on the basis of elevated hemoglobin A1c, in the absence of prior personal or family history. Autoimmune or type 1 diabetes mellitus was ruled out with normal levels of anti-glutamic acid decarboxylase 65 (GAD65) antibody, zinc transporter 8 (ZnT8) antibody, and islet antigen-2 (IA-2) antibody.ConclusionsThis case report highlights the importance of recognizing rare but serious adverse events related to immunotherapy and incorporation of appropriate tools for early identification and management in national cancer treatment guidelines.

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“…This mechanistic difference may help partially explain the fact that nivolumab is more tolerable and is associated with a significantly lower risk of severe treatment-related adverse events, compared to docetaxel. However, nivolumab is not entirely safe, as previous studies have revealed associations with increased risks of thyroid dysfunction, fulminant type 1 diabetes mellitus, and vitiligo 17,22,23 . Therefore, additional detailed clinical information and biomarkers are needed to predict these treatment-related adverse events in patients who receive nivolumab 17 .…”

Section: Discussionmentioning

confidence: 91%

Comparing the Adverse Event Profiles of Nivolumab and Docetaxel in Previously-treated or Refractory Advanced Non-small Cell Lung Cancer: A Meta-analysis of Two Phase 3 Trials

Koichi:筆頭著者:責任著者

Murata

Kusumoto

et al. 2017

Showa Univ J Med Sci

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: Nivolumab has recently been approved as a second-line treatment for squamous and non-squamous advanced non-small cell lung cancers NSCLC . However, no studies have statistically evaluated the adverse event profiles for nivolumab and conventional second-line agents, such as docetaxel. Thus, there is unmet medical need for statistical analysis comparing the adverse effects of nivolumab and docdetaxel in patients with advanced NSCLC. This meta-analysis evaluated the non-inferiority and superiority of the adverse event profiles for nivolumab and docetaxel in patients with previously-treated or refractory advanced NSCLC. The meta-analysis examined two phase 3 trials and compared the incidences of drug-induced adverse events for the nivolumab-treated and docetaxeltreated patient groups. The primary outcomes were the odds ratios ORs and 95 con dence intervals CIs for any adverse event, fatigue, nausea, decreased appetite, diarrhea, myalgia, anemia, alopecia, neutropenia, febrile neutropenia, and leukopenia. Compared to docetaxel, the adverse event profile for nivolumab was non-inferior and superior for any adverse event OR, 0.27 ; 95 CI, fatigue OR, 0.44 ; 95 CI, nausea OR, 0.37 ; 95 CI, decreased appetite OR, 0.58 ; 95 CI, diarrhea OR, 0.29 ; 95 CI, myalgia OR, 0.18 ; 95 CI, anemia OR, 0.08 ; 95 CI, alopecia OR, 0.01 ; 95 CI, neutropenia OR, 0.01 ; 95 CI, febrile neutropenia OR, 0.02 ; 95 CI, and leukopenia OR, 0.04 ; 95 CI, . These results suggest that, compared to docetaxel, nivolumab may be better tolerated for managing advanced NSCLC.

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Fulminant type 1 diabetes mellitus with anti‐programmed cell death‐1 therapy

Cited by 144 publications

References 10 publications

Acute Hyperglycemia Associated with Anti-Cancer Medication

Acute Hyperglycemia Associated with Anti-Cancer Medication

Combined checkpoint inhibitor therapy causing diabetic ketoacidosis in metastatic melanoma

Comparing the Adverse Event Profiles of Nivolumab and Docetaxel in Previously-treated or Refractory Advanced Non-small Cell Lung Cancer: A Meta-analysis of Two Phase 3 Trials

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