Tumor mutational load predicts survival after immunotherapy across multiple cancer types
By Robert Samstein, Chung-Han Lee, A. Shoushtari, M. Hellmann, Ronglai Shen, Y. Janjigian, D. Barron, A. Zehir, E. Jordan, A. Omuro and 47 more. Nature Genetics, 2019
3,368 citations recorded by the source corpus.
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. Analysis of advanced cancer patients treated with immune-checkpoint inhibitors shows that tumor mutational burden, as assessed by targeted next-generation sequencing, predicts survival after immunotherapy across multiple cancer types.
Subfields: Cancer Research, Oncology, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/53985c0660a211334aa64d2154335a9022eab9e8
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Citations in the corpus
- The role of PD-L1 expression as a predictive biomarker: an analysis of all US Food and Drug Administration (FDA) approvals of immune checkpoint inhibitors (2019, background): “However, some challenges for clinical implementation of TMB include defining uniform detection methods and appropriate thresholds for response by tumor type [22].”
- Harnessing multimodal data integration to advance precision oncology (2021, background): “Higher-order genomic properties such as tumour mutational burden (TMB) 53 , endogenous mutational processes such as MSI 54 and homologous recombination deficiency (HRD), and large-scale features such as whole genome duplication 55 are also clinically meaningful.”
- Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition (2021, positive): “As a validation cohort, we obtained processed copy-number segment and overall survival data from n = 1,600 cases from CPI-treated patients profiled using the MSK-IMPACT panel (Consortium, 2017; Samstein et al., 2019) (referred to hereafter as the MSK1600 cohort; RECIST response outcome data were not”