PMID- 34986342
OWN - NLM
STAT- MEDLINE
DCOM- 20220222
LR  - 20220222
IS  - 1097-4180 (Electronic)
IS  - 1074-7613 (Linking)
VI  - 55
IP  - 1
DP  - 2022 Jan 11
TI  - Germline HLA landscape does not predict efficacy of pembrolizumab monotherapy 
      across solid tumor types.
PG  - 56-64.e4
LID - S1074-7613(21)00542-2 [pii]
LID - 10.1016/j.immuni.2021.12.006 [doi]
AB  - We evaluated the impact of class I and class II human leukocyte antigen (HLA) 
      genotypes, heterozygosity, and diversity on the efficacy of pembrolizumab. 
      Seventeen pembrolizumab clinical trials across eight tumor types and one basket 
      trial in patients with advanced solid tumors were included (n > 3,500 analyzed). 
      Germline DNA was genotyped using a custom genotyping array. HLA diversity 
      (measured by heterozygosity and evolutionary divergence) across class I loci was 
      not associated with improved response to pembrolizumab, either within each tumor 
      type evaluated or across all patients. Similarly, HLA heterozygosity at each 
      class I and class II gene was not associated with response to pembrolizumab after 
      accounting for the number of tests conducted. No conclusive association between 
      HLA genotype and response to pembrolizumab was identified in this dataset. 
      Germline HLA genotype or diversity alone is not an important independent 
      determinant of response to pembrolizumab and should not be used for clinical 
      decision-making in patients treated with pembrolizumab.
CI  - Copyright (c) 2021. Published by Elsevier Inc.
FAU - Chhibber, Aparna
AU  - Chhibber A
AD  - Department of Biomarker and Genome Sciences, Merck & Co., Kenilworth, NJ 07033, 
      USA.
FAU - Huang, Lingkang
AU  - Huang L
AD  - Department of Biostatistics and Research Decision Sciences, Merck & Co., 
      Kenilworth, NJ 07033, USA.
FAU - Zhang, Hong
AU  - Zhang H
AD  - Department of Biostatistics and Research Decision Sciences, Merck & Co., 
      Kenilworth, NJ 07033, USA.
FAU - Xu, Jialin
AU  - Xu J
AD  - Department of Biostatistics and Research Decision Sciences, Merck & Co., 
      Kenilworth, NJ 07033, USA.
FAU - Cristescu, Razvan
AU  - Cristescu R
AD  - Department of Biomarker and Genome Sciences, Merck & Co., Kenilworth, NJ 07033, 
      USA.
FAU - Liu, Xiaoqiao
AU  - Liu X
AD  - Department of Biomarker and Genome Sciences, Merck & Co., Kenilworth, NJ 07033, 
      USA.
FAU - Mehrotra, Devan V
AU  - Mehrotra DV
AD  - Department of Biostatistics and Research Decision Sciences, Merck & Co., 
      Kenilworth, NJ 07033, USA.
FAU - Shen, Judong
AU  - Shen J
AD  - Department of Biostatistics and Research Decision Sciences, Merck & Co., 
      Kenilworth, NJ 07033, USA.
FAU - Shaw, Peter M
AU  - Shaw PM
AD  - Department of Biomarker and Genome Sciences, Merck & Co., Kenilworth, NJ 07033, 
      USA. Electronic address: peter_shaw3@merck.com.
FAU - Hellmann, Matthew D
AU  - Hellmann MD
AD  - Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 
      10065, USA; Department of Medicine, Weill Cornell Medical College, New York, NY 
      10065, USA. Electronic address: hellmanm@mskcc.org.
FAU - Snyder, Alexandra
AU  - Snyder A
AD  - Department of Medical Oncology, Merck & Co., Kenilworth, NJ 07033, USA. 
      Electronic address: snyderalex@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220105
PL  - United States
TA  - Immunity
JT  - Immunity
JID - 9432918
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (HLA Antigens)
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - 0 (PDCD1 protein, human)
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - DPT0O3T46P (pembrolizumab)
SB  - IM
CIN - Immunity. 2022 Jan 11;55(1):3-6. PMID: 35021056
MH  - Age Factors
MH  - Antibodies, Monoclonal, Humanized/*therapeutic use
MH  - Female
MH  - Genetic Association Studies
MH  - *Genotype
MH  - Germ-Line Mutation/*genetics
MH  - HLA Antigens/*genetics
MH  - Heterozygote
MH  - Humans
MH  - Immune Checkpoint Inhibitors/*therapeutic use
MH  - Male
MH  - Neoplasms/diagnosis/*drug therapy/mortality
MH  - Polymorphism, Genetic
MH  - Prognosis
MH  - Programmed Cell Death 1 Receptor/antagonists & inhibitors
MH  - Sex Factors
MH  - Survival Analysis
MH  - Treatment Outcome
OTO - NOTNLM
OT  - HLA
OT  - PD-1
OT  - checkpoint
OT  - germline
OT  - heterozygosity
OT  - human leukocyte antigen
OT  - pan tumor
OT  - pembrolizumab
COIS- Declaration of interests A.C. was an employee of Merck Sharp & Dohme, a 
      subsidiary of Merck & Co., Kenilworth, NJ, USA, when the analysis was conducted 
      and is a stockholder of Merck & Co., Kenilworth, NJ, USA, and a current employee 
      of Bristol Myers Squibb. L.H. is an employee of Merck Sharp & Dohme, a subsidiary 
      of Merck & Co., Kenilworth, NJ, USA, and is a stockholder of Merck & Co., 
      Kenilworth, NJ, USA. H.Z. is an employee of Merck Sharp & Dohme, a subsidiary of 
      Merck & Co., Kenilworth, NJ, USA, and is a stockholder of Merck & Co., 
      Kenilworth, NJ, USA. J.X. was an employee of Merck Sharp & Dohme, a subsidiary of 
      Merck & Co., Kenilworth, NJ, USA, when the analysis was conducted and is a 
      stockholder of Merck & Co., Kenilworth, NJ, USA. R.C. is an employee of Merck 
      Sharp & Dohme, a subsidiary of Merck & Co., Kenilworth, NJ, USA, and is a 
      stockholder of Merck & Co., Kenilworth, NJ, USA. X.L. is an employee of Merck 
      Sharp & Dohme, a subsidiary of Merck & Co., Kenilworth, NJ, USA. D.V.M. is an 
      employee of Merck Sharp & Dohme, a subsidiary of Merck & Co., Kenilworth, NJ, 
      USA, and is a stockholder of Merck & Co., Kenilworth, NJ, USA. J.S. is an 
      employee of Merck Sharp & Dohme, a subsidiary of Merck & Co., Kenilworth, NJ, 
      USA, and is a stockholder of Merck & Co., Kenilworth, NJ, USA. P.M.S. is an 
      employee of Merck Sharp & Dohme, a subsidiary of Merck & Co., Kenilworth, NJ, 
      USA, and is a stockholder of Merck & Co., Kenilworth, NJ, USA. M.D.H. reports 
      grants from Bristol Myers Squibb and personal fees from Achilles, Adagene, 
      Adicet, Arcus, Astra Zeneca, Blueprint, Bristol Myers Squibb, DaVolterra, Eli 
      Lilly, Genentech/Roche, Genzyme/Sanofi, Immunai, Instil Bio, Janssen, Mana 
      Therapeutics, Merck Sharp & Dohme, a subsidiary of Merck & Co., Kenilworth, NJ, 
      USA, Mirati, Natera, PACT Pharma, Shattuck Labs, and Regeneron, as well as equity 
      options from Arcus, Factorial, Immunai, and Shattuck Labs. A patent filed by 
      Memorial Sloan Kettering related to the use of tumor mutational burden to predict 
      response to immunotherapy (PCT/US2015/062208) is pending and licensed by PGDx. 
      M.D.H. is also supported, in part, by the Damon Runyon Cancer Research Foundation 
      (grant no. CI-98-18) and the Memorial Sloan Kettering Cancer Center support 
      grant/core grant no P30 CA008748. A.S. was an employee of Merck Sharp & Dohme, a 
      subsidiary of Merck & Co., Kenilworth, NJ, USA, when the analysis was conducted 
      and is a stockholder of Merck & Co., Kenilworth, NJ, USA, and a current employee 
      of Two River.
EDAT- 2022/01/06 06:00
MHDA- 2022/02/23 06:00
CRDT- 2022/01/05 20:06
PHST- 2021/03/24 00:00 [received]
PHST- 2021/10/21 00:00 [revised]
PHST- 2021/12/08 00:00 [accepted]
PHST- 2022/01/06 06:00 [pubmed]
PHST- 2022/02/23 06:00 [medline]
PHST- 2022/01/05 20:06 [entrez]
AID - S1074-7613(21)00542-2 [pii]
AID - 10.1016/j.immuni.2021.12.006 [doi]
PST - ppublish
SO  - Immunity. 2022 Jan 11;55(1):56-64.e4. doi: 10.1016/j.immuni.2021.12.006. Epub 
      2022 Jan 5.