PMID- 31488221
OWN - NLM
STAT- MEDLINE
DCOM- 20200813
LR  - 20200813
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 7
IP  - 1
DP  - 2019 Sep 5
TI  - 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.
PG  - 241
LID - 10.1186/s40425-019-0713-y [doi]
LID - 241
AB  - BACKGROUND: 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. CASE: 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 ss-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. CONCLUSION: 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.
FAU - Gunjur, Ashray
AU  - Gunjur A
AUID- ORCID: 0000-0001-9713-1872
AD  - Department of Medical Oncology, Austin Health, Melbourne, Australia. 
      ashray.gunjur@austin.org.au.
FAU - Klein, Oliver
AU  - Klein O
AD  - Department of Medical Oncology, Austin Health, Melbourne, Australia.
AD  - Olivia Newton-John Cancer Research Institute, School of Cancer Medicine, La Trobe 
      University, Melbourne, Australia.
FAU - Kee, Damien
AU  - Kee D
AD  - Department of Medical Oncology, Austin Health, Melbourne, Australia.
AD  - Department of Medicine, University of Melbourne, Melbourne, Australia.
FAU - Cebon, Jonathan
AU  - Cebon J
AD  - Department of Medical Oncology, Austin Health, Melbourne, Australia.
AD  - Olivia Newton-John Cancer Research Institute, School of Cancer Medicine, La Trobe 
      University, Melbourne, Australia.
LA  - eng
PT  - Case Reports
PT  - Journal Article
PT  - Review
DEP - 20190905
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/*adverse effects
MH  - Antineoplastic Agents, Immunological/*adverse effects
MH  - Female
MH  - Humans
MH  - Melanoma/*drug therapy/pathology
MH  - Polyendocrinopathies, Autoimmune/chemically induced/*pathology
MH  - Prognosis
MH  - Programmed Cell Death 1 Receptor/*antagonists & inhibitors
PMC - PMC6729071
OTO - NOTNLM
OT  - Diabetes mellitus
OT  - Hypoadrenalism
OT  - Hypothyroidism
OT  - Immune checkpoint inhibitor
OT  - PD1 inhibitor
OT  - Pembrolizumab
OT  - Poly-endocrinopathy
COIS- The authors declare they have no competing interests.
EDAT- 2019/09/07 06:00
MHDA- 2020/08/14 06:00
PMCR- 2019/09/05
CRDT- 2019/09/07 06:00
PHST- 2019/05/30 00:00 [received]
PHST- 2019/08/21 00:00 [accepted]
PHST- 2019/09/07 06:00 [entrez]
PHST- 2019/09/07 06:00 [pubmed]
PHST- 2020/08/14 06:00 [medline]
PHST- 2019/09/05 00:00 [pmc-release]
AID - 10.1186/s40425-019-0713-y [pii]
AID - 713 [pii]
AID - 10.1186/s40425-019-0713-y [doi]
PST - epublish
SO  - J Immunother Cancer. 2019 Sep 5;7(1):241. doi: 10.1186/s40425-019-0713-y.