PMID- 30529903
OWN - NLM
STAT- MEDLINE
DCOM- 20200504
LR  - 20200505
IS  - 1879-0852 (Electronic)
IS  - 0959-8049 (Linking)
VI  - 107
DP  - 2019 Jan
TI  - Human leukocyte antigen variation is associated with adverse events of checkpoint 
      inhibitors.
PG  - 8-14
LID - S0959-8049(18)31470-9 [pii]
LID - 10.1016/j.ejca.2018.11.009 [doi]
AB  - BACKGROUND: Checkpoint inhibitors (CIs) are highly effective but can induce 
      severe immune-related adverse events (irAEs), which cannot be predicted. We 
      investigated whether human leukocyte antigen (HLA) genes predispose to developing 
      of irAEs during therapy and thus hold a predictive role. METHODS: We established 
      a prospective observational single-centre study and collected data from patients 
      with either metastatic non-small cell lung cancer (NSCLC) or metastatic melanoma, 
      who were treated with anti-PD-1 (programmed cell death receptor 1), anti-CTLA4 
      (cytotoxic T-lymphocyte-associated protein 4) or both CIs combined. Data 
      include irAEs and ranges from 15th July 2016 until 10th May 2018. In addition, we 
      performed HLA typing via next generation sequencing. RESULTS: We enrolled 102 
      patients (median [range] age, 68 [62-74] years) with metastatic cancer in our 
      study who received CI therapy. Of these patients, 59 (58%) developed one or more 
      irAEs, among which pruritus (n = 32 (54%)) and rash (n = 24 (41%)) had the 
      highest rates. We did not find evidence for a single HLA gene being associated 
      with all irAEs (all P > .05). When assessing each irAE individually, we found a 
      significant association between HLA-DRB1*11:01 and pruritus (OR = 4.53, 
      X(2)(1,95) = 9.45, P < .01) as well as a nominally significant additive 
      association between HLA-DQB1*03:01 and colitis (OR = 3.94, X(2)(1,95) = 5.67, 
      P = .017). CONCLUSIONS: The presence of two HLA alleles that are known to 
      predispose to autoimmune diseases were associated with the development of 
      pruritus or colitis during therapy, suggesting a genetic aetiology of irAEs. 
      Larger genome-wide association studies should be performed to confirm our 
      findings.
CI  - Copyright (c) 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.
FAU - Hasan Ali, Omar
AU  - Hasan Ali O
AD  - Department of Dermatology, University Hospital of Zurich, CH-8091, Zurich, 
      Switzerland; Institute of Immunobiology, Kantonsspital St.Gallen, CH-9007, St. 
      Gallen, Switzerland.
FAU - Berner, Fiamma
AU  - Berner F
AD  - Institute of Immunobiology, Kantonsspital St.Gallen, CH-9007, St. Gallen, 
      Switzerland.
FAU - Bomze, David
AU  - Bomze D
AD  - Institute of Immunobiology, Kantonsspital St.Gallen, CH-9007, St. Gallen, 
      Switzerland.
FAU - Fassler, Mirjam
AU  - Fassler M
AD  - Institute of Immunobiology, Kantonsspital St.Gallen, CH-9007, St. Gallen, 
      Switzerland.
FAU - Diem, Stefan
AU  - Diem S
AD  - Department of Oncology and Hematology, Kantonsspital St. Gallen, CH-9007, St. 
      Gallen, Switzerland; Department of Oncology and Hematology, Hospital of Grabs, 
      CH-9472, Grabs, Switzerland.
FAU - Cozzio, Antonio
AU  - Cozzio A
AD  - Department of Dermatology, Kantonsspital St. Gallen, CH-9007, St. Gallen, 
      Switzerland.
FAU - Jorger, Markus
AU  - Jorger M
AD  - Department of Oncology and Hematology, Kantonsspital St. Gallen, CH-9007, St. 
      Gallen, Switzerland.
FAU - Fruh, Martin
AU  - Fruh M
AD  - Department of Oncology and Hematology, Kantonsspital St. Gallen, CH-9007, St. 
      Gallen, Switzerland.
FAU - Driessen, Christoph
AU  - Driessen C
AD  - Department of Oncology and Hematology, Kantonsspital St. Gallen, CH-9007, St. 
      Gallen, Switzerland.
FAU - Lenz, Tobias L
AU  - Lenz TL
AD  - Research Group for Evolutionary Immunogenomics, Max Planck Institute for 
      Evolutionary Biology, D-24306, Plon, Germany.
FAU - Flatz, Lukas
AU  - Flatz L
AD  - Department of Dermatology, University Hospital of Zurich, CH-8091, Zurich, 
      Switzerland; Institute of Immunobiology, Kantonsspital St.Gallen, CH-9007, St. 
      Gallen, Switzerland; Department of Oncology and Hematology, Kantonsspital St. 
      Gallen, CH-9007, St. Gallen, Switzerland; Department of Dermatology, 
      Kantonsspital St. Gallen, CH-9007, St. Gallen, Switzerland. Electronic address: 
      lukas.flatz@kssg.ch.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20181207
PL  - England
TA  - Eur J Cancer
JT  - European journal of cancer (Oxford, England : 1990)
JID - 9005373
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (HLA-DQ beta-Chains)
RN  - 0 (HLA-DQB1 antigen)
SB  - IM
MH  - Aged
MH  - Antineoplastic Agents, Immunological/*adverse effects
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/pathology
MH  - Drug-Related Side Effects and Adverse Reactions/*diagnosis/etiology/genetics
MH  - Female
MH  - Follow-Up Studies
MH  - *Genetic Variation
MH  - HLA-DQ beta-Chains/*genetics
MH  - Humans
MH  - Lung Neoplasms/*drug therapy/pathology
MH  - Male
MH  - Melanoma/*drug therapy/pathology
MH  - Middle Aged
MH  - Prognosis
MH  - Prospective Studies
OTO - NOTNLM
OT  - Cancer immunotherapy
OT  - Human leukocyte antigen
OT  - Immune-related adverse events
OT  - Melanoma
OT  - Non-small cell lung cancer
OT  - Therapeutic marker
EDAT- 2018/12/12 06:00
MHDA- 2020/05/06 06:00
CRDT- 2018/12/12 06:00
PHST- 2018/08/22 00:00 [received]
PHST- 2018/11/01 00:00 [accepted]
PHST- 2018/12/12 06:00 [pubmed]
PHST- 2020/05/06 06:00 [medline]
PHST- 2018/12/12 06:00 [entrez]
AID - S0959-8049(18)31470-9 [pii]
AID - 10.1016/j.ejca.2018.11.009 [doi]
PST - ppublish
SO  - Eur J Cancer. 2019 Jan;107:8-14. doi: 10.1016/j.ejca.2018.11.009. Epub 2018 Dec 
      7.