Anti-programmed cell death protein 1 (anti-PD1) immunotherapy induced autoimmune polyendocrine syndrome type II (APS-2): a case report and review of the literature.

Anti-programmed cell death protein 1 (anti-PD1) immunotherapy induced autoimmune polyendocrine syndrome type II (APS-2): a case report and review of the literature.

Publication date: Sep 05, 2019

Autoimmune polyendocrine syndrome type II (APS-2) is a rare constellation of autoimmune hypoadrenalism, thyroid dysfunction and/or type 1 diabetes (T1DM), usually occurring in the 3rd or 4th decades and associated with a human leukocyte antigen (HLA) DR3 or DR4 serotype. We detail the first report of an elderly woman developing the full triad of APS-2 shortly after commencing anti-programmed cell death protein 1 (anti-PD1) immune checkpoint inhibition for unresectable melanoma and review the literature for similar presentations secondary to anti-PD1 axis therapy.

A 78-year-old female with advanced unresectable BRAF wild-type melanoma was treated with pembrolizumab (2 mg/kg 3-weekly). Three weeks following the first dose she developed fulminant autoimmune diabetes, with an initially low C-peptide denoting rapid destruction of cDF-islet cells. Following stabilisation of her diabetes, two further doses of pembrolizumab was administered. She then represented with symptomatic hypoadrenalism and hypothyroidism, consistent with APS-2. Her HLA class II genotype was HLA-DRB1*04.16 (DR4 serotype), a recognised association with this syndrome. Her melanoma responded rapidly to anti-PD1 therapy, and a complete response (CR) was attained after four doses of pembrolizumab. Treatment was discontinued and her CR is ongoing.

This is the first report of the full triad of APS-2 developing in a genetically susceptible individual at the age of 78 after treatment with an anti-PD1 agent. Although scarcely reported, a literature review of similar reports seems to indicate a predilection for this syndrome in patients with HLA-DR4 serotypes. HLA Class II typing is not routinely recommended, but may provide useful predictive information for patients at risk of poly-endocrinopathy even in patients without a relevant personal or family history. Additional studies are required to determine if such testing would be useful and/or cost effective.

Gunjur, A., Klein, O., Kee, D., and Cebon, J. Anti-programmed cell death protein 1 (anti-PD1) immunotherapy induced autoimmune polyendocrine syndrome type II (APS-2): a case report and review of the literature. 24028. 2019 J Immunother Cancer (7):1.

Concepts Keywords
Antigen Syndrome melanoma
Autoimmune Hypoadrenalism hypothyroidism
BRAF Fulminant autoimmune diabetes
C Peptide Diabetes T1DM
Constellation Immunotherapy
Diabetes Medicine
DR3 Medical specialties
Endocrinopathy Clinical medicine
Genotype Immune system
HLA Immunology
Hypoadrenalism Autoimmune diseases
Hypothyroidism Endocrine diseases
Immunotherapy Cancer treatments
Islet Cells Checkpoint inhibitor
Leukocyte Pembrolizumab
Melanoma Autoimmune polyendocrine syndrome
Serotype T cell
Serotypes Genotype
Susceptible Individual
Syndrome
Thyroid
Triad
Wild Type

Semantics

Type Source Name
disease DOID Diabetes mellitus
disease MESH Diabetes mellitus
gene UNIPROT SPATA2
disease DOID syndrome
disease MESH syndrome
disease DOID hypothyroidism
disease MESH hypothyroidism
drug DRUGBANK Pembrolizumab
gene UNIPROT BRAF
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
gene UNIPROT TNFRSF10A
gene UNIPROT HLA-DRB1
gene UNIPROT TNFRSF25
disease MESH type 1 diabetes
disease MESH hypoadrenalism
gene UNIPROT SH2B2
gene UNIPROT KLK3
drug DRUGBANK Adenosine 5′-phosphosulfate
disease DOID autoimmune polyendocrine syndrome
gene UNIPROT PDCD1

Original Article

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