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      Tumor mutational load predicts survival after immunotherapy across multiple cancer types

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      Nature Genetics
      Springer Science and Business Media LLC

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          Abstract

          Immune checkpoint inhibitor (ICI) treatments benefit some patients with metastatic cancers, but predictive biomarkers are needed. Findings in select 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 1662 advanced cancer patients treated with ICI, and 5371 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 OS (HR 0.52; p=1.6 ×10 −6 ). 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.

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          Author and article information

          Journal
          Nature Genetics
          Nat Genet
          Springer Science and Business Media LLC
          1061-4036
          1546-1718
          February 2019
          January 14 2019
          February 2019
          : 51
          : 2
          : 202-206
          Article
          10.1038/s41588-018-0312-8
          6365097
          30643254
          ccca6bc6-f6e5-4a72-b7fe-3bfbf880c208
          © 2019

          http://www.springer.com/tdm

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