The association between tumor mutational burden and prognosis is dependent on treatment context

Cristina Valero; Mark Lee; Douglas Hoen; Jingming Wang; Zaineb Nadeem; Neal Patel; Michael A. Postow; Alexander N. Shoushtari; George Plitas; Vinod P. Balachandran; J. Joshua Smith; Aimee M. Crago; Kara C. Long Roche; Daniel W. Kelly; Robert M. Samstein; Satshil Rana; Ian Ganly; Richard J. Wong; A. Ari Hakimi; Michael F. Berger; Ahmet Zehir; David B. Solit; Marc Ladanyi; Nadeem Riaz; Timothy A. Chan; Venkatraman E. Seshan; Luc G.T. Morris

doi:10.1038/s41588-020-00752-4

The association between tumor mutational burden and prognosis is dependent on treatment context

Cristina Valero
, Mark Lee
, Douglas Hoen
, Jingming Wang
, Zaineb Nadeem
, Neal Patel
, Michael A. Postow
, Alexander N. Shoushtari
, George Plitas
, Vinod P. Balachandran
, J. Joshua Smith
, Aimee M. Crago
, Kara C. Long Roche
, Daniel W. Kelly
, Robert M. Samstein
, Satshil Rana
, Ian Ganly
, Richard J. Wong
, A. Ari Hakimi
, Michael F. Berger

Ahmet Zehir, David B. Solit, Marc Ladanyi, Nadeem Riaz, Timothy A. Chan, Venkatraman E. Seshan, Luc G.T. Morris

Research output: Contribution to journal › Article › peer-review

210 Scopus citations

Abstract

In multiple cancer types, high tumor mutational burden (TMB) is associated with longer survival after treatment with immune checkpoint inhibitors (ICIs). The association of TMB with survival outside of the immunotherapy context is poorly understood. We analyzed 10,233 patients (80% non-ICI-treated, 20% ICI-treated) with 17 cancer types before/without ICI treatment or after ICI treatment. In non-ICI-treated patients, higher TMB (higher percentile within cancer type) was not associated with better prognosis; in fact, in many cancer types, higher TMB was associated with poorer survival, in contrast to ICI-treated patients in whom higher TMB was associated with longer survival.

Original language	English
Pages (from-to)	11-15
Number of pages	5
Journal	Nature Genetics
Volume	53
Issue number	1
DOIs	https://doi.org/10.1038/s41588-020-00752-4
State	Published - Jan 2021
Externally published	Yes

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Valero, C., Lee, M., Hoen, D., Wang, J., Nadeem, Z., Patel, N., Postow, M. A., Shoushtari, A. N., Plitas, G., Balachandran, V. P., Smith, J. J., Crago, A. M., Long Roche, K. C., Kelly, D. W., Samstein, R. M., Rana, S., Ganly, I., Wong, R. J., Hakimi, A. A., ... Morris, L. G. T. (2021). The association between tumor mutational burden and prognosis is dependent on treatment context. Nature Genetics, 53(1), 11-15. https://doi.org/10.1038/s41588-020-00752-4

@article{577ab3130c594c788fb1e3c5b01c9884,

title = "The association between tumor mutational burden and prognosis is dependent on treatment context",

abstract = "In multiple cancer types, high tumor mutational burden (TMB) is associated with longer survival after treatment with immune checkpoint inhibitors (ICIs). The association of TMB with survival outside of the immunotherapy context is poorly understood. We analyzed 10,233 patients (80\% non-ICI-treated, 20\% ICI-treated) with 17 cancer types before/without ICI treatment or after ICI treatment. In non-ICI-treated patients, higher TMB (higher percentile within cancer type) was not associated with better prognosis; in fact, in many cancer types, higher TMB was associated with poorer survival, in contrast to ICI-treated patients in whom higher TMB was associated with longer survival.",

author = "Cristina Valero and Mark Lee and Douglas Hoen and Jingming Wang and Zaineb Nadeem and Neal Patel and Postow, \{Michael A.\} and Shoushtari, \{Alexander N.\} and George Plitas and Balachandran, \{Vinod P.\} and Smith, \{J. Joshua\} and Crago, \{Aimee M.\} and \{Long Roche\}, \{Kara C.\} and Kelly, \{Daniel W.\} and Samstein, \{Robert M.\} and Satshil Rana and Ian Ganly and Wong, \{Richard J.\} and Hakimi, \{A. Ari\} and Berger, \{Michael F.\} and Ahmet Zehir and Solit, \{David B.\} and Marc Ladanyi and Nadeem Riaz and Chan, \{Timothy A.\} and Seshan, \{Venkatraman E.\} and Morris, \{Luc G.T.\}",

note = "Publisher Copyright: {\textcopyright} 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.",

year = "2021",

month = jan,

doi = "10.1038/s41588-020-00752-4",

language = "English",

volume = "53",

pages = "11--15",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

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}

Valero, C, Lee, M, Hoen, D, Wang, J, Nadeem, Z, Patel, N, Postow, MA, Shoushtari, AN, Plitas, G, Balachandran, VP, Smith, JJ, Crago, AM, Long Roche, KC, Kelly, DW, Samstein, RM, Rana, S, Ganly, I, Wong, RJ, Hakimi, AA, Berger, MF, Zehir, A, Solit, DB, Ladanyi, M, Riaz, N, Chan, TA, Seshan, VE & Morris, LGT 2021, 'The association between tumor mutational burden and prognosis is dependent on treatment context', Nature Genetics, vol. 53, no. 1, pp. 11-15. https://doi.org/10.1038/s41588-020-00752-4

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T1 - The association between tumor mutational burden and prognosis is dependent on treatment context

AU - Valero, Cristina

AU - Lee, Mark

AU - Hoen, Douglas

AU - Wang, Jingming

AU - Nadeem, Zaineb

AU - Patel, Neal

AU - Postow, Michael A.

AU - Shoushtari, Alexander N.

AU - Plitas, George

AU - Balachandran, Vinod P.

AU - Smith, J. Joshua

AU - Crago, Aimee M.

AU - Long Roche, Kara C.

AU - Kelly, Daniel W.

AU - Samstein, Robert M.

AU - Rana, Satshil

AU - Ganly, Ian

AU - Wong, Richard J.

AU - Hakimi, A. Ari

AU - Berger, Michael F.

AU - Zehir, Ahmet

AU - Solit, David B.

AU - Ladanyi, Marc

AU - Riaz, Nadeem

AU - Chan, Timothy A.

AU - Seshan, Venkatraman E.

AU - Morris, Luc G.T.

PY - 2021/1

Y1 - 2021/1

N2 - In multiple cancer types, high tumor mutational burden (TMB) is associated with longer survival after treatment with immune checkpoint inhibitors (ICIs). The association of TMB with survival outside of the immunotherapy context is poorly understood. We analyzed 10,233 patients (80% non-ICI-treated, 20% ICI-treated) with 17 cancer types before/without ICI treatment or after ICI treatment. In non-ICI-treated patients, higher TMB (higher percentile within cancer type) was not associated with better prognosis; in fact, in many cancer types, higher TMB was associated with poorer survival, in contrast to ICI-treated patients in whom higher TMB was associated with longer survival.

AB - In multiple cancer types, high tumor mutational burden (TMB) is associated with longer survival after treatment with immune checkpoint inhibitors (ICIs). The association of TMB with survival outside of the immunotherapy context is poorly understood. We analyzed 10,233 patients (80% non-ICI-treated, 20% ICI-treated) with 17 cancer types before/without ICI treatment or after ICI treatment. In non-ICI-treated patients, higher TMB (higher percentile within cancer type) was not associated with better prognosis; in fact, in many cancer types, higher TMB was associated with poorer survival, in contrast to ICI-treated patients in whom higher TMB was associated with longer survival.

UR - https://www.scopus.com/pages/publications/85098624908

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DO - 10.1038/s41588-020-00752-4

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AN - SCOPUS:85098624908

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VL - 53

SP - 11

EP - 15

JO - Nature Genetics

JF - Nature Genetics

IS - 1

ER -

The association between tumor mutational burden and prognosis is dependent on treatment context

Abstract

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