PMID- 35689896
OWN - NLM
STAT- MEDLINE
DCOM- 20220810
LR  - 20220817
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 170
DP  - 2022 Aug
TI  - HLA-I diversity and tumor mutational burden by comprehensive next-generation 
      sequencing as predictive biomarkers for the treatment of non-small cell lung 
      cancer with PD-(L)1 inhibitors.
PG  - 1-10
LID - S0169-5002(22)00464-0 [pii]
LID - 10.1016/j.lungcan.2022.05.019 [doi]
AB  - OBJECTIVES: Immune checkpoint inhibitors (ICIs) improved outcomes in non-small 
      cell lung cancer (NSCLC) patients. We report the predictive utility of human 
      leukocyte antigen class I (HLA-I) diversity and tumor mutational burden (TMB) by 
      comprehensive next-generation sequencing. METHODS: 126 patients were included. 
      TMB high was defined as >/= 10 nonsynonymous mutations/Mb. Patients exhibit high 
      HLA-I diversity if at least one locus was in the upper 15th percentile for DNA 
      alignment scores. RESULTS: No difference in response rate (RR; 44.4% versus 
      30.9%; p = 0.1741) or 6-month survival rate (SR; 75.6% versus 77.8%; p = 0.7765) 
      was noted between HLA-I high diversity and low diversity patients. HLA-I high 
      diversity patients did significantly more often exhibit durable clinical benefit 
      (DCB), defined as response or stable disease lasting minimally 6 months (64.4% 
      [29/45] versus 43.2% [35/81]; p = 0.0223). TMB high patients exhibited higher RR 
      (49.1% versus 25.4%; p = 0.0084) and SR 6 months after start ICI (85.5% versus 
      70.4%; p = 0.0468) than TMB low patients. The proportion of patients with DCB, 
      did not differ significantly between TMB high and low subgroups (60.0% [33/55] 
      versus 42.3% [30/71]; p = 0.0755). Patients with combined dual high TMB and HLA-I 
      diversity had higher RR (63.2% versus 22.2%; p = 0.0033), but SR at 6 months did 
      not differ significantly (84.2% versus 64,4%; p = 0.1536). A significantly higher 
      rate of patients experienced DCB in dual high compared to the dual low group 
      (73.7% [14/19] versus 35.6% [16/45]; p = 0.0052). Triple positive patients (high 
      TMB and HLA-I diversity and PD-L1 positive) had higher RR (63.6% versus 0.0%; 
      p = 0.0047) and SR at 6 months (100% versus 66.7%; p = 0.0378) compared to 
      triple-negative patients. CONCLUSION: HLA-I diversity was able to predict durable 
      clinical benefit in ICI treated NSCLC patients, but failed to confirm as a 
      predictor of response or survival. TMB confirmed as a predictive biomarker.
CI  - Copyright (c) 2022 The Author(s). Published by Elsevier B.V. All rights reserved.
FAU - Cuppens, Kristof
AU  - Cuppens K
AD  - Dept. Pulmonology and Thoracic Oncology, Jessa Hospital, Hasselt, Belgium; Dept. 
      Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands; 
      Faculty of Medicine and Life Sciences - LCRC, Hasselt University, Diepenbeek, 
      Belgium. Electronic address: Kristof.cuppens@jessazh.be.
FAU - Baas, Paul
AU  - Baas P
AD  - Dept. Thoracic Oncology, The Netherlands Cancer Institute, Amsterdam, the 
      Netherlands.
FAU - Geerdens, Ellen
AU  - Geerdens E
AD  - Laboratory for Molecular Diagnostics, Dept Laboratory Medicine, Jessa Hospital, 
      Hasselt, Belgium.
FAU - Cruys, Bert
AU  - Cruys B
AD  - Laboratory for Molecular Diagnostics, Dept Laboratory Medicine, Jessa Hospital, 
      Hasselt, Belgium.
FAU - Froyen, Guy
AU  - Froyen G
AD  - Laboratory for Molecular Diagnostics, Dept Laboratory Medicine, Jessa Hospital, 
      Hasselt, Belgium.
FAU - Decoster, Lynn
AU  - Decoster L
AD  - Dept. Pulmonology, AZ Turnhout, Turnhout, Belgium.
FAU - Thomeer, Michiel
AU  - Thomeer M
AD  - Faculty of Medicine and Life Sciences - LCRC, Hasselt University, Diepenbeek, 
      Belgium; Dept. Respiratory Medicine, Ziekenhuis Oost Limburg, Genk, Belgium.
FAU - Maes, Brigitte
AU  - Maes B
AD  - Laboratory for Molecular Diagnostics, Dept Laboratory Medicine, Jessa Hospital, 
      Hasselt, Belgium.
LA  - eng
PT  - Journal Article
DEP - 20220531
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (HLA Antigens)
SB  - IM
MH  - B7-H1 Antigen/genetics
MH  - Biomarkers, Tumor/genetics
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology
MH  - HLA Antigens
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - *Lung Neoplasms/drug therapy/genetics/pathology
MH  - Mutation
OTO - NOTNLM
OT  - HED
OT  - HLA-I diversity
OT  - HLA-I evolutionary divergence
OT  - Non-small cell lung cancer
OT  - PD-1 immunotherapy
OT  - TSO500
OT  - Tumor mutational burden
EDAT- 2022/06/12 06:00
MHDA- 2022/08/11 06:00
CRDT- 2022/06/11 18:17
PHST- 2022/01/16 00:00 [received]
PHST- 2022/05/26 00:00 [revised]
PHST- 2022/05/28 00:00 [accepted]
PHST- 2022/06/12 06:00 [pubmed]
PHST- 2022/08/11 06:00 [medline]
PHST- 2022/06/11 18:17 [entrez]
AID - S0169-5002(22)00464-0 [pii]
AID - 10.1016/j.lungcan.2022.05.019 [doi]
PST - ppublish
SO  - Lung Cancer. 2022 Aug;170:1-10. doi: 10.1016/j.lungcan.2022.05.019. Epub 2022 May 
      31.