PMID- 33229510
OWN - NLM
STAT- MEDLINE
DCOM- 20210916
LR  - 20240330
IS  - 2051-1426 (Electronic)
IS  - 2051-1426 (Linking)
VI  - 8
IP  - 2
DP  - 2020 Nov
TI  - Prognostic value of HLA-I homozygosity in patients with non-small cell lung 
      cancer treated with single agent immunotherapy.
LID - 10.1136/jitc-2020-001620 [doi]
LID - e001620
AB  - BACKGROUND: We aimed to assess the impact of genomic human leukocyte antigen 
      (HLA)-I/II homozygosity on the survival benefit of patients with unresectable 
      locally advanced, metastatic non-small lung cancer treated by single-agent 
      programmed cell death protein-1/programmed death ligand 1 (PD1/PDL1) inhibitors. 
      METHODS: We collected blood from 170 patients with advanced lung cancer treated 
      with immunotherapy at two major oncology centers in Western Australia. Genomic 
      DNA was extracted from white blood cells and used for HLA-I/II high-resolution 
      typing. HLA-I/II homozygosity was tested for association with survival outcomes. 
      Univariable and multivariable Cox regression models were constructed to determine 
      whether HLA homozygosity was an independent prognostic factor affecting Overall 
      Survival (OS) and Progression Free Survival (PFS). We also investigated the 
      association between individual HLA-A and -B supertypes with OS. RESULTS: 
      Homozygosity at HLA-I loci, but not HLA-II, was significantly associated with 
      shorter OS (HR=2.17, 95% CI 1.13 to 4.17, p=0.02) in both univariable and 
      multivariable analysis. The effect of HLA-I homozygosity in OS was particularly 
      relevant for patients with tumors expressing PDL1 >/=50% (HR=3.93, 95% CI 1.30 to 
      11.85, p<0.001). The adverse effect of HLA-I homozygosity on PFS was only 
      apparent after controlling for interactions between PDL1 status and HLA-I 
      genotype (HR=2.21, 95% CI 1.04 to 4.70, p=0.038). The presence of HLA-A02 
      supertype was the only HLA-I supertype to be associated with improved OS 
      (HR=0.56, 95% CI 0.34 to 0.93, p=0.023). CONCLUSION: Our results suggest that 
      homozygosity at >/=1 HLA-I loci is associated with short OS and PFS in patients 
      with advanced non-small cell lung cancer with PDL1 >/=50% treated with single-agent 
      immunotherapy. Carriers of HLA-A02 supertype reported better survival outcomes in 
      this cohort of patients.
CI  - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Abed, Afaf
AU  - Abed A
AUID- ORCID: 0000-0001-7506-3362
AD  - School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western 
      Australia, Australia afaf.abed@health.wa.gov.au.
AD  - Linear Clinical Research, Nedlands, Western Australia, Australia.
AD  - Department of Medical Oncology, Fiona Stanley Hospital, Murdoch, Western 
      Australia, Australia.
FAU - Calapre, Leslie
AU  - Calapre L
AD  - School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western 
      Australia, Australia.
FAU - Lo, Johnny
AU  - Lo J
AD  - School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western 
      Australia, Australia.
FAU - Correia, Suzana
AU  - Correia S
AD  - Department of Medical Oncology, Fiona Stanley Hospital, Murdoch, Western 
      Australia, Australia.
FAU - Bowyer, Samantha
AU  - Bowyer S
AD  - Linear Clinical Research, Nedlands, Western Australia, Australia.
AD  - Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western 
      Australia, Australia.
FAU - Chopra, Abha
AU  - Chopra A
AD  - Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, 
      Western Australia, Australia.
FAU - Watson, Mark
AU  - Watson M
AD  - Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, 
      Western Australia, Australia.
FAU - Khattak, Muhammad Adnan
AU  - Khattak MA
AD  - School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western 
      Australia, Australia.
AD  - Department of Medical Oncology, Fiona Stanley Hospital, Murdoch, Western 
      Australia, Australia.
FAU - Millward, Michael
AU  - Millward M
AD  - Linear Clinical Research, Nedlands, Western Australia, Australia.
AD  - Department of Medical Oncology, Sir Charles Gairdner Hospital, Nedlands, Western 
      Australia, Australia.
AD  - School of Medicine, The University of Western Australia, Perth, Western 
      Australia, Australia.
FAU - Gray, Elin Solomonovna
AU  - Gray ES
AUID- ORCID: 0000-0002-8613-3570
AD  - School of Medical and Health Sciences, Edith Cowan University, Joondalup, Western 
      Australia, Australia.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Immunother Cancer
JT  - Journal for immunotherapy of cancer
JID - 101620585
RN  - 0 (HLA Antigens)
SB  - IM
MH  - Aged
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/mortality/pathology
MH  - Female
MH  - HLA Antigens/*genetics
MH  - Humans
MH  - Immunotherapy/*methods
MH  - Lung Neoplasms/*genetics/mortality/pathology
MH  - Male
MH  - Prognosis
MH  - Progression-Free Survival
PMC - PMC7684824
OTO - NOTNLM
OT  - biomarkers
OT  - immunotherapy
OT  - lung neoplasms
OT  - tumor
COIS- Competing interests: MM sits on advisory boards for Merck Sharp and Dohme (MSD), 
      Bristol-Myers Squibb (BMS) and AstraZeneca (AZ). MAK sits on advisory boards of 
      MSD, BMS and Merck Serono. ESG has received travel support from MSD.
EDAT- 2020/11/25 06:00
MHDA- 2021/09/18 06:00
PMCR- 2020/11/23
CRDT- 2020/11/24 05:56
PHST- 2020/10/27 00:00 [accepted]
PHST- 2020/11/24 05:56 [entrez]
PHST- 2020/11/25 06:00 [pubmed]
PHST- 2021/09/18 06:00 [medline]
PHST- 2020/11/23 00:00 [pmc-release]
AID - jitc-2020-001620 [pii]
AID - 10.1136/jitc-2020-001620 [doi]
PST - ppublish
SO  - J Immunother Cancer. 2020 Nov;8(2):e001620. doi: 10.1136/jitc-2020-001620.