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Nat Genet. 2019 Feb;51(2):202-206. doi: 10.1038/s41588-018-0312-8. Epub 2019 Jan 14.

Tumor mutational load predicts survival after immunotherapy across multiple cancer types.

Author information

1
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
2
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
3
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
4
Department of Medicine, Weill Cornell Medical Center, New York, NY, USA.
5
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
6
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
7
Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
8
Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
9
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
10
Department of Medicine, Columbia University Medical Center, New York, NY, USA.
11
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. solitd@mskcc.org.
12
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA. solitd@mskcc.org.
13
Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. chant@mskcc.org.
14
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. chant@mskcc.org.
15
Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA. chant@mskcc.org.
16
Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. morrisl@mskcc.org.
17
Immunogenomics and Precision Oncology Platform, Memorial Sloan Kettering Cancer Center, New York, NY, USA. morrisl@mskcc.org.
18
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. morrisl@mskcc.org.

Abstract

Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in selected cancer types suggest that tumor mutational burden (TMB) may predict clinical response to ICI. To examine this association more broadly, we analyzed the clinical and genomic data of 1,662 advanced cancer patients treated with ICI, and 5,371 non-ICI-treated patients, whose tumors underwent targeted next-generation sequencing (MSK-IMPACT). Among all patients, higher somatic TMB (highest 20% in each histology) was associated with better overall survival. For most cancer histologies, an association between higher TMB and improved survival was observed. The TMB cutpoints associated with improved survival varied markedly between cancer types. These data indicate that TMB is associated with improved survival in patients receiving ICI across a wide variety of cancer types, but that there may not be one universal definition of high TMB.

PMID:
30643254
PMCID:
PMC6365097
[Available on 2020-02-01]
DOI:
10.1038/s41588-018-0312-8
[Indexed for MEDLINE]

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