Development Of Type 1 Diabetes After Cancer Immunotherapy

Abstract

Objective: Nivolumab, anti-programmed cell death 1 monoclonal antibody, is a newly Food and Drug Administration-approved biologic for the treatment of metastatic melanoma. New indications for treatment of other cancers have been recently granted. Nivolumab package insert reads: "Warnings and Precautions: immunemediated pneumonitis, colitis, hepatitis, nephritis and renal dysfunction, hypothyroidism and hyperthyroidism may occur." Development of type 1 diabetes as an adverse event was not documented in the New England Journal of Medicine article that introduced its successful use for melanoma treatment. Methods: We present the case of an adult patient who developed autoimmune diabetes after treatment with nivolumab, accompanied by the presence of high serum titers of glutamic acid decarboxylase 65 (GAD65) isoform antibodies and a clinical presentation of diabetic ketoacidosis. Results: Although endocrine autoimmunity has been described following treatment with nivolumab, type 1 diabetes has only been shown after the treatment of 2 patients with melanoma that happened to be antibody (GAD65, insulin, and islet cell antibody) negative. Conclusion: Clinicians prescribing this drug need to be aware of this life-threatening adverse effect. At a minimum, patient education should be offered to every patient treated with this biologic. (AACE Clinical Case Rep. 2017;3:e242-e245) Abbreviations: GAD65 = glutamic acid decarboxylase 65; PD-1 = programmed cell death 1

Immune checkpoint inhibitors and type 1 diabetes mellitus: a case report and systematic review

“…Supplementary Table 1 (see section on supplementary data given at the end of this article) provides an overview of our search terms. Additionally, the authors reviewed the reference lists of the included articles (4, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68) and identified five additional cases (69, 70, 71, 72). The following data were extracted from each manuscript: author, year of publication, age, gender and ethnicity of the patient, cancer type, checkpoint inhibitor therapy, number of cycles of therapy, prior immunotherapy, relevant past medical history (PMH), presence of diabetic ketoacidosis, glycemia, glycated hemoglobin, C-peptide, islet autoantibodies, lipase, other irAE and HLA genotype.…”

Clinical characteristics and outcomes of immune checkpoint inhibitor-induced diabetes mellitus

“…Baseline characteristics are presented in Table 2 . In addition to our patients, 171 cases were identified [ 7 , 8 , [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , [24] , [25] , [26] , [27] , [28] , [29] , [30] , [31] , [32] , [33] , [34] , [35] , [36] , [37] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] , [46] , [47] , [48] , [49] , [50] , [51] , [52] , [53] , [54] , [55] , [56] , [57] , [58] , [59] , [60] , [61] , [62] , [63] , [64] , [65] , [66] , [67] , [68] , [69] , [70] , [71] , [72] , [73] , [74] , [...…”

Pembrolizumab and diabetes: a case of diabetic ketoacidosis in a patient with metastatic melanoma

“…8 The current hypothesis is that PD-1 inhibitors cause T1DM by activation of autoreactive CD8+ T-cells that have the ability both to survive and to destroy β-cells. 9 Recent reports suggest that the use of PD-1 and PD-L-1 agents may lead to a 1% chance of diabetes mellitus (DM) occurrence, including new-onset T1DM or worsening of type 2 DM (T2DM). 4,10 In patients who develop T1DM, the mechanism appears similar to the permanent autoimmune process of T1DM, but with faster, aggressive destruction of beta islet cells, likely mediated by T-cells, requiring insulin replacement.…”