Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition

Barzin Y. Nabet; Mohammad S. Esfahani; Everett J. Moding; Emily G. Hamilton; Jacob J. Chabon; Hira Rizvi; Chloe B. Steen; Aadel A. Chaudhuri; Chih Long Liu; Angela B. Hui; Diego Almanza; Henning Stehr; Linda Gojenola; Rene F. Bonilla; Michael C. Jin; Young Jun Jeon; Diane Tseng; Cailian Liu; Taha Merghoub; Joel W. Neal; Heather A. Wakelee; Sukhmani K. Padda; Kavitha J. Ramchandran; Millie Das; Andrew J. Plodkowski; Christopher Yoo; Emily L. Chen; Ryan B. Ko; Aaron M. Newman; Matthew D. Hellmann; Ash A. Alizadeh; Maximilian Diehn

doi:10.1016/j.cell.2020.09.001

Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition

Barzin Y. Nabet, Mohammad S. Esfahani, Everett J. Moding, Emily G. Hamilton, Jacob J. Chabon, Hira Rizvi, Chloe B. Steen, Aadel A. Chaudhuri, Chih Long Liu, Angela B. Hui, Diego Almanza, Henning Stehr, Linda Gojenola, Rene F. Bonilla, Michael C. Jin, Young Jun Jeon, Diane Tseng, Cailian Liu, Taha Merghoub, Joel W. NealHeather A. Wakelee, Sukhmani K. Padda, Kavitha J. Ramchandran, Millie Das, Andrew J. Plodkowski, Christopher Yoo, Emily L. Chen, Ryan B. Ko, Aaron M. Newman, Matthew D. Hellmann, Ash A. Alizadeh, Maximilian Diehn

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

223 Scopus citations

Abstract

Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs.

Original language	English
Pages (from-to)	363-376.e13
Journal	Cell
Volume	183
Issue number	2
DOIs	https://doi.org/10.1016/j.cell.2020.09.001
State	Published - Oct 15 2020

Keywords

circulating tumor DNA
immune checkpoint inhibition
immunotherapy
liquid biopsy
non-small cell lung cancer
response classification

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10.1016/j.cell.2020.09.001

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Nabet, B. Y., Esfahani, M. S., Moding, E. J., Hamilton, E. G., Chabon, J. J., Rizvi, H., Steen, C. B., Chaudhuri, A. A., Liu, C. L., Hui, A. B., Almanza, D., Stehr, H., Gojenola, L., Bonilla, R. F., Jin, M. C., Jeon, Y. J., Tseng, D., Liu, C., Merghoub, T., ... Diehn, M. (2020). Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition. Cell, 183(2), 363-376.e13. https://doi.org/10.1016/j.cell.2020.09.001

@article{5e4e67c694d44427bdd8802e9e91fdac,

title = "Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition",

abstract = "Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs.",

keywords = "circulating tumor DNA, immune checkpoint inhibition, immunotherapy, liquid biopsy, non-small cell lung cancer, response classification",

author = "Nabet, {Barzin Y.} and Esfahani, {Mohammad S.} and Moding, {Everett J.} and Hamilton, {Emily G.} and Chabon, {Jacob J.} and Hira Rizvi and Steen, {Chloe B.} and Chaudhuri, {Aadel A.} and Liu, {Chih Long} and Hui, {Angela B.} and Diego Almanza and Henning Stehr and Linda Gojenola and Bonilla, {Rene F.} and Jin, {Michael C.} and Jeon, {Young Jun} and Diane Tseng and Cailian Liu and Taha Merghoub and Neal, {Joel W.} and Wakelee, {Heather A.} and Padda, {Sukhmani K.} and Ramchandran, {Kavitha J.} and Millie Das and Plodkowski, {Andrew J.} and Christopher Yoo and Chen, {Emily L.} and Ko, {Ryan B.} and Newman, {Aaron M.} and Hellmann, {Matthew D.} and Alizadeh, {Ash A.} and Maximilian Diehn",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",

year = "2020",

month = oct,

day = "15",

doi = "10.1016/j.cell.2020.09.001",

language = "English",

volume = "183",

pages = "363--376.e13",

journal = "Cell",

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Nabet, BY, Esfahani, MS, Moding, EJ, Hamilton, EG, Chabon, JJ, Rizvi, H, Steen, CB, Chaudhuri, AA, Liu, CL, Hui, AB, Almanza, D, Stehr, H, Gojenola, L, Bonilla, RF, Jin, MC, Jeon, YJ, Tseng, D, Liu, C, Merghoub, T, Neal, JW, Wakelee, HA, Padda, SK, Ramchandran, KJ, Das, M, Plodkowski, AJ, Yoo, C, Chen, EL, Ko, RB, Newman, AM, Hellmann, MD, Alizadeh, AA & Diehn, M 2020, 'Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition', Cell, vol. 183, no. 2, pp. 363-376.e13. https://doi.org/10.1016/j.cell.2020.09.001

TY - JOUR

T1 - Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition

AU - Nabet, Barzin Y.

AU - Esfahani, Mohammad S.

AU - Moding, Everett J.

AU - Hamilton, Emily G.

AU - Chabon, Jacob J.

AU - Rizvi, Hira

AU - Steen, Chloe B.

AU - Chaudhuri, Aadel A.

AU - Liu, Chih Long

AU - Hui, Angela B.

AU - Almanza, Diego

AU - Stehr, Henning

AU - Gojenola, Linda

AU - Bonilla, Rene F.

AU - Jin, Michael C.

AU - Jeon, Young Jun

AU - Tseng, Diane

AU - Liu, Cailian

AU - Merghoub, Taha

AU - Neal, Joel W.

AU - Wakelee, Heather A.

AU - Padda, Sukhmani K.

AU - Ramchandran, Kavitha J.

AU - Das, Millie

AU - Plodkowski, Andrew J.

AU - Yoo, Christopher

AU - Chen, Emily L.

AU - Ko, Ryan B.

AU - Newman, Aaron M.

AU - Hellmann, Matthew D.

AU - Alizadeh, Ash A.

AU - Diehn, Maximilian

PY - 2020/10/15

Y1 - 2020/10/15

N2 - Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs.

AB - Although treatment of non-small cell lung cancer (NSCLC) with immune checkpoint inhibitors (ICIs) can produce remarkably durable responses, most patients develop early disease progression. Furthermore, initial response assessment by conventional imaging is often unable to identify which patients will achieve durable clinical benefit (DCB). Here, we demonstrate that pre-treatment circulating tumor DNA (ctDNA) and peripheral CD8 T cell levels are independently associated with DCB. We further show that ctDNA dynamics after a single infusion can aid in identification of patients who will achieve DCB. Integrating these determinants, we developed and validated an entirely noninvasive multiparameter assay (DIREct-On, Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On-treatment) that robustly predicts which patients will achieve DCB with higher accuracy than any individual feature. Taken together, these results demonstrate that integrated ctDNA and circulating immune cell profiling can provide accurate, noninvasive, and early forecasting of ultimate outcomes for NSCLC patients receiving ICIs.

KW - circulating tumor DNA

KW - immune checkpoint inhibition

KW - immunotherapy

KW - liquid biopsy

KW - non-small cell lung cancer

KW - response classification

UR - http://www.scopus.com/inward/record.url?scp=85092497602&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2020.09.001

DO - 10.1016/j.cell.2020.09.001

M3 - Article

C2 - 33007267

AN - SCOPUS:85092497602

SN - 0092-8674

VL - 183

SP - 363-376.e13

JO - Cell

JF - Cell

IS - 2

ER -

Noninvasive Early Identification of Therapeutic Benefit from Immune Checkpoint Inhibition

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Keywords

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