@article{18dec998b9f945b68e4898f87605402b,
title = "Improved prediction of immune checkpoint blockade efficacy across multiple cancer types",
abstract = "Only a fraction of patients with cancer respond to immune checkpoint blockade (ICB) treatment, but current decision-making procedures have limited accuracy. In this study, we developed a machine learning model to predict ICB response by integrating genomic, molecular, demographic and clinical data from a comprehensively curated cohort (MSK-IMPACT) with 1,479 patients treated with ICB across 16 different cancer types. In a retrospective analysis, the model achieved high sensitivity and specificity in predicting clinical response to immunotherapy and predicted both overall survival and progression-free survival in the test data across different cancer types. Our model significantly outperformed predictions based on tumor mutational burden, which was recently approved by the U.S. Food and Drug Administration for this purpose1. Additionally, the model provides quantitative assessments of the model features that are most salient for the predictions. We anticipate that this approach will substantially improve clinical decision-making in immunotherapy and inform future interventions.",
author = "Diego Chowell and Yoo, {Seong Keun} and Cristina Valero and Alessandro Pastore and Chirag Krishna and Mark Lee and Douglas Hoen and Hongyu Shi and Kelly, {Daniel W.} and Neal Patel and Vladimir Makarov and Xiaoxiao Ma and Lynda Vuong and Sabio, {Erich Y.} and Kate Weiss and Fengshen Kuo and Lenz, {Tobias L.} and Samstein, {Robert M.} and Nadeem Riaz and Adusumilli, {Prasad S.} and Balachandran, {Vinod P.} and George Plitas and {Ari Hakimi}, A. and Omar Abdel-Wahab and Shoushtari, {Alexander N.} and Postow, {Michael A.} and Motzer, {Robert J.} and Marc Ladanyi and Ahmet Zehir and Berger, {Michael F.} and Mithat G{\"o}nen and Morris, {Luc G.T.} and Nils Weinhold and Chan, {Timothy A.}",
note = "Funding Information: T.A.C. is a co-founder of Gritstone Oncology and holds equity. T.A.C. holds equity in An2H. T.A.C. acknowledges grant funding from Bristol Myers Squibb, AstraZeneca, Illumina, Pfizer, An2H and Eisai. T.A.C. has served as an advisor for Bristol Myers, MedImmune, Squibb, Illumina, Eisai, AstraZeneca and An2H. T.A.C., L.G.T.M. and D.C. hold ownership of intellectual property on using tumor mutational burden to predict immunotherapy response, with a pending patent, which has been licensed to PGDx. M.A.P. reports consulting fees from Bristol Myers Squibb, Merck, Array BioPharma, Novartis, Incyte, NewLink Genetics, Aduro and Eisai; honoraria from Bristol Myers Squibb and Merck; and institutional support from RGenix, Infinity, Bristol Myers Squibb, Merck, Array BioPharma, Novartis and AstraZeneca. M.L. has received advisory board compensation from Merck and Bristol Myers Squibb. The remaining authors declare no competing interests. Funding Information: We thank the Chan lab and members of the Immunogenomics and Precision Oncology Platform for advice and input. This work was supported, in part, by NIH R35 CA232097 (T.A.C.), NIH RO1 CA205426 (T.A.C.), the PaineWebber Chair (T.A.C.), NIH/NCI Cancer Center Support Grant (P30 CA008748), Fundaci{\'o}n Alfonso Mart{\'i}n Escudero (C.V.), NIH K08 DE024774, NIH R01 DE027738, the Sebastian Nativo Fund and the Jayme and Peter Flowers Fund (to L.G.T.M.). Funding Information: We thank the Chan lab and members of the Immunogenomics and Precision Oncology Platform for advice and input. This work was supported, in part, by NIH R35 CA232097 (T.A.C.), NIH RO1 CA205426 (T.A.C.), the PaineWebber Chair (T.A.C.), NIH/NCI Cancer Center Support Grant (P30 CA008748), Fundaci?n Alfonso Mart?n Escudero (C.V.), NIH K08 DE024774, NIH R01 DE027738, the Sebastian Nativo Fund and the Jayme and Peter Flowers Fund (to L.G.T.M.). Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",
year = "2022",
month = apr,
doi = "10.1038/s41587-021-01070-8",
language = "English",
volume = "40",
pages = "499--506",
journal = "Nature Biotechnology",
issn = "1087-0156",
publisher = "Nature Publishing Group",
number = "4",
}