A case of multiple immune toxicities from Ipilimumab and pembrolizumab treatment

Humayun, Malik Asif; Poole, Ruth

doi:10.14310/horm.2002.1656

Cited by 20 publications

(9 citation statements)

References 7 publications

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“…All the cases using anti-PD-1 mAbs were reported post-marketing, most 2–3 years after their approval in 2014. There were 6 cases of polyglandular endocrinopathies involving T1DM - plus anterior hypopituitarism [75, 95], plus anterior hypopituitarism + Graves’ disease [76], plus, thyroiditis [129, 130], plus primary hypothyroidism [132], and plus hyperthyroidism progressing to hypothyroidism [76, 130].…”

Section: Resultsmentioning

confidence: 99%

Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports

Tan

Iyengar

Mizokami-Stout

et al. 2019

Clin Diabetes Endocrinol

147

149

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BackgroundSince 2011 six immune checkpoint inhibitors (ICI) have been approved to treat patients with many advanced solid tumor and hematological malignancies to improve their prognosis. Case reports of their endocrine immune-related adverse events [irAEs]) are increasingly published as more real-world patients with these malignancies are treated with these drugs. They alert physicians of a drug’s AEs (which may change during a drug’s life cycle) and contribute to post-marketing safety surveillance. Using a modified framework of Arksey and O’Malley, we conducted a scoping review of the spectrum and characteristics of ICI-induced endocrinopathies case reports before and after ICIs are marketed.MethodsIn July 2017, we searched, without date and language restrictions, 4 citation databases for ICI-induced endocrinopathies. We also hand-searched articles’ references, contents of relevant journals, and ran supplemental searches to capture recent reports through January 2018. For this study, a case should have information on type of cancer, type of ICI, clinical presentation, biochemical tests, treatment plus temporal association of ICI initiation with endocrinopathies. Two endocrinologists independently extracted the data which were then summarized and categorized.ResultsOne hundred seventy nine articles reported 451 cases of ICI-induced endocrinopathies - 222 hypopituitarism, 152 thyroid disorders, 66 diabetes mellitus, 6 primary adrenal insufficiencies, 1 ACTH-dependent Cushing’s syndrome, 1 hypoparathyroidism and 3 diabetes insipidus cases. Their clinical presentations reflect hormone excess or deficiency. Some were asymptomatic and others life-threatening. One or more endocrine glands could be affected. Polyglandular endocrinopathies could present simultaneously or in sequence. Many occur within 5 months of therapy initiation; a few occurred after ICI was stopped. Mostly irreversible, they required long-term hormone replacement. High dose steroids were used when non-endocrine AEs coexisted or as therapy in adrenal insufficiency. There was variability of information in the case reports but all met the study criteria to make a diagnosis.ConclusionsThe spectrum of ICI-induced endocrinopathies is wide (5 glands affected) and their presentation varied (12 endocrinopathies). Clinical reasoning integrating clinical, biochemical and treatment information is needed to properly diagnose and manage them. Physicians should be vigilant for their occurrence and be able to diagnose, investigate and manage them appropriately at onset and follow-up.Electronic supplementary materialThe online version of this article (10.1186/s40842-018-0073-4) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports

Tan

Iyengar

Mizokami-Stout

et al. 2019

Clin Diabetes Endocrinol

147

149

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“…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.…”

Section: Methodsmentioning

confidence: 99%

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

Filette

Pen

Decoster

et al. 2019

European Journal of Endocrinology

188

196

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Objective To better define the rare adverse event (AE) of diabetes mellitus associated with immune checkpoint inhibitors (ICIs). Design and methods We report the case of a lung cancer patient with diabetic ketoacidosis (DKA) and autoimmune thyroiditis during pembrolizumab treatment. We provide a systematic review of all published cases (PubMed/Web of Science/Cochrane, through November 2018) of autoimmune diabetes mellitus related to blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4)-, programmed cell death 1 (PD-1) receptor or its ligand (PD-L1) or combination (ICI) therapy. Results Our literature search identified 90 patient cases (our case excluded). Most patients were treated with anti-PD-1 or anti-PD-L1 as monotherapy (79%) or in combination with CTLA-4 blockade (15%). On average, diabetes mellitus was diagnosed after 4.5 cycles; earlier for combination ICI at 2.7 cycles. Early-onset diabetes mellitus (after one or two cycles) was observed during all treatment regimens. Diabetic ketoacidosis was present in 71%, while elevated lipase levels were detected in 52% (13/25). Islet autoantibodies were positive in 53% of patients with a predominance of glutamic acid decarboxylase antibodies. Susceptible HLA genotypes were present in 65% (mostly DR4). Thyroid dysfunction was the most frequent other endocrine AE at 24% incidence in this patient population. Conclusion ICI-related diabetes mellitus is a rare but often life-threatening metabolic urgency of which health-care professionals and patients should be aware. Close monitoring of blood glucose and prompt endocrine investigation in case of hyperglycemia is advisable. Predisposing factors such as HLA genotype might explain why some individuals are at risk.

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“…The six cases were reviewed and there salient points were compiled in Table 1 [ 6 - 11 ]. There was no sex predilection with three females and three males affected and the average age at presentation was 58 years old.…”

Section: Literature Retrievedmentioning

confidence: 99%

Autoimmune Diabetes Associated With Pembrolizumab: A Review of Published Case Reports

et al. 2018

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The utility of immunotherapy, such as pembrolizumab, is becoming essential in the treatment of certain cancers. Pembrolizumab works through binding of programmed cell death 1 receptor that blocks the binding of the programmed cell death ligand 1 and is commonly used in non-small cell lung cancer and melanoma. Pembrolizumab has been reported to be associated with multiple adverse reactions such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes; however, pembrolizumab causing type 1 diabetes was only reported in 0.1% of the patients in clinical trials. A review of the literature generated 1,001 unique citations of which six reported cases of autoimmune diabetes associated with pembrolizumab were selected and compared. Review of the cases showed no sexual predilection and the average age of onset was 58 years old. The majority of the patients were treated for melanoma (5/6 cases), initially presented with diabetic ketoacidosis (4/6 cases), and had at one point taken ipilimumab (4/6 cases). There was no association found between the number of treatments received and the development of diabetes. With the increasing use of pembrolizumab in cancer treatment regular blood glucose monitoring during treatment, especially in patients who had also taken ipilimumab, may prevent the onset of this life-threatening complication.

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A case of multiple immune toxicities from Ipilimumab and pembrolizumab treatment

Cited by 20 publications

References 7 publications

Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports

Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports

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

Autoimmune Diabetes Associated With Pembrolizumab: A Review of Published Case Reports

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