Interplay of Immunosuppression and Immunotherapy among Patients with Cancer and COVID-19

Ziad Bakouny; Chris Labaki; Punita Grover; Joy Awosika; Shuchi Gulati; Chih Yuan Hsu; Saif I. Alimohamed; Babar Bashir; Stephanie Berg; Mehmet A. Bilen; Daniel Bowles; Cecilia Castellano; Aakash Desai; Arielle Elkrief; Omar E. Eton; Leslie A. Fecher; Daniel Flora; Matthew D. Galsky; Margaret E. Gatti-Mays; Alicia Gesenhues; Michael J. Glover; Dharmesh Gopalakrishnan; Shilpa Gupta; Thorvardur R. Halfdanarson; Brandon Hayes-Lattin; Mohamed Hendawi; Emily Hsu; Clara Hwang; Roman Jandarov; Chinmay Jani; Douglas B. Johnson; Monika Joshi; Hina Khan; Shaheer A. Khan; Natalie Knox; Vadim S. Koshkin; Amit A. Kulkarni; Daniel H. Kwon; Sara Matar; Rana R. McKay; Sanjay Mishra; Feras A. Moria; Amanda Nizam; Nora L. Nock; Taylor K. Nonato; Justin Panasci; Lauren Pomerantz; Andrew J. Portuguese; Destie Provenzano; Matthew Puc; Yuan J. Rao; Terence D. Rhodes; Gregory J. Riely; Jacob J. Ripp; Andrea V. Rivera; Erika Ruiz-Garcia; Andrew L. Schmidt; Adam J. Schoenfeld; Gary K. Schwartz; Sumit A. Shah; Justin Shaya; Suki Subbiah; Lisa M. Tachiki; Matthew D. Tucker; Melissa Valdez-Reyes; Lisa B. Weissmann; Michael T. Wotman; Elizabeth M. Wulff-Burchfield; Zhuoer Xie; Yuanchu James Yang; Michael A. Thompson; Dimpy P. Shah; Jeremy L. Warner; Yu Shyr; Toni K. Choueiri; Trisha M. Wise-Draper

doi:10.1001/jamaoncol.2022.5357

Interplay of Immunosuppression and Immunotherapy among Patients with Cancer and COVID-19

Ziad Bakouny, Chris Labaki, Punita Grover, Joy Awosika, Shuchi Gulati, Chih Yuan Hsu, Saif I. Alimohamed, Babar Bashir, Stephanie Berg, Mehmet A. Bilen, Daniel Bowles, Cecilia Castellano, Aakash Desai, Arielle Elkrief, Omar E. Eton, Leslie A. Fecher, Daniel Flora, Matthew D. Galsky, Margaret E. Gatti-Mays, Alicia GesenhuesMichael J. Glover, Dharmesh Gopalakrishnan, Shilpa Gupta, Thorvardur R. Halfdanarson, Brandon Hayes-Lattin, Mohamed Hendawi, Emily Hsu, Clara Hwang, Roman Jandarov, Chinmay Jani, Douglas B. Johnson, Monika Joshi, Hina Khan, Shaheer A. Khan, Natalie Knox, Vadim S. Koshkin, Amit A. Kulkarni, Daniel H. Kwon, Sara Matar, Rana R. McKay, Sanjay Mishra, Feras A. Moria, Amanda Nizam, Nora L. Nock, Taylor K. Nonato, Justin Panasci, Lauren Pomerantz, Andrew J. Portuguese, Destie Provenzano, Matthew Puc, Yuan J. Rao, Terence D. Rhodes, Gregory J. Riely, Jacob J. Ripp, Andrea V. Rivera, Erika Ruiz-Garcia, Andrew L. Schmidt, Adam J. Schoenfeld, Gary K. Schwartz, Sumit A. Shah, Justin Shaya, Suki Subbiah, Lisa M. Tachiki, Matthew D. Tucker, Melissa Valdez-Reyes, Lisa B. Weissmann, Michael T. Wotman, Elizabeth M. Wulff-Burchfield, Zhuoer Xie, Yuanchu James Yang, Michael A. Thompson, Dimpy P. Shah, Jeremy L. Warner, Yu Shyr, Toni K. Choueiri, Trisha M. Wise-Draper

Medical Oncology

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

Abstract

Importance: Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective: To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included 12046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings. Exposures: Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO). Main Outcomes and Measures: The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm. Results: The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79). Conclusions and Relevance: This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm. Trial Registration: ClinicalTrials.gov Identifier: NCT04354701.

Original language	English (US)
Pages (from-to)	128-134
Number of pages	7
Journal	JAMA Oncology
Volume	9
Issue number	1
DOIs	https://doi.org/10.1001/jamaoncol.2022.5357
State	Published - Jan 19 2023

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1001/jamaoncol.2022.5357

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Bakouny, Z., Labaki, C., Grover, P., Awosika, J., Gulati, S., Hsu, C. Y., Alimohamed, S. I., Bashir, B., Berg, S., Bilen, M. A., Bowles, D., Castellano, C., Desai, A., Elkrief, A., Eton, O. E., Fecher, L. A., Flora, D., Galsky, M. D., Gatti-Mays, M. E., ... Wise-Draper, T. M. (2023). Interplay of Immunosuppression and Immunotherapy among Patients with Cancer and COVID-19. JAMA Oncology, 9(1), 128-134. https://doi.org/10.1001/jamaoncol.2022.5357

Bakouny, Z, Labaki, C, Grover, P, Awosika, J, Gulati, S, Hsu, CY, Alimohamed, SI, Bashir, B, Berg, S, Bilen, MA, Bowles, D, Castellano, C, Desai, A, Elkrief, A, Eton, OE, Fecher, LA, Flora, D, Galsky, MD, Gatti-Mays, ME, Gesenhues, A, Glover, MJ, Gopalakrishnan, D, Gupta, S, Halfdanarson, TR, Hayes-Lattin, B, Hendawi, M, Hsu, E, Hwang, C, Jandarov, R, Jani, C, Johnson, DB, Joshi, M, Khan, H, Khan, SA, Knox, N, Koshkin, VS, Kulkarni, AA, Kwon, DH, Matar, S, McKay, RR, Mishra, S, Moria, FA, Nizam, A, Nock, NL, Nonato, TK, Panasci, J, Pomerantz, L, Portuguese, AJ, Provenzano, D, Puc, M, Rao, YJ, Rhodes, TD, Riely, GJ, Ripp, JJ, Rivera, AV, Ruiz-Garcia, E, Schmidt, AL, Schoenfeld, AJ, Schwartz, GK, Shah, SA, Shaya, J, Subbiah, S, Tachiki, LM, Tucker, MD, Valdez-Reyes, M, Weissmann, LB, Wotman, MT, Wulff-Burchfield, EM, Xie, Z, Yang, YJ, Thompson, MA, Shah, DP, Warner, JL, Shyr, Y, Choueiri, TK & Wise-Draper, TM 2023, 'Interplay of Immunosuppression and Immunotherapy among Patients with Cancer and COVID-19', JAMA Oncology, vol. 9, no. 1, pp. 128-134. https://doi.org/10.1001/jamaoncol.2022.5357

@article{18a647fbed524b51ae98d68bc803c449,

title = "Interplay of Immunosuppression and Immunotherapy among Patients with Cancer and COVID-19",

abstract = "Importance: Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective: To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included 12046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings. Exposures: Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO). Main Outcomes and Measures: The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm. Results: The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79). Conclusions and Relevance: This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm. Trial Registration: ClinicalTrials.gov Identifier: NCT04354701.",

author = "Ziad Bakouny and Chris Labaki and Punita Grover and Joy Awosika and Shuchi Gulati and Hsu, {Chih Yuan} and Alimohamed, {Saif I.} and Babar Bashir and Stephanie Berg and Bilen, {Mehmet A.} and Daniel Bowles and Cecilia Castellano and Aakash Desai and Arielle Elkrief and Eton, {Omar E.} and Fecher, {Leslie A.} and Daniel Flora and Galsky, {Matthew D.} and Gatti-Mays, {Margaret E.} and Alicia Gesenhues and Glover, {Michael J.} and Dharmesh Gopalakrishnan and Shilpa Gupta and Halfdanarson, {Thorvardur R.} and Brandon Hayes-Lattin and Mohamed Hendawi and Emily Hsu and Clara Hwang and Roman Jandarov and Chinmay Jani and Johnson, {Douglas B.} and Monika Joshi and Hina Khan and Khan, {Shaheer A.} and Natalie Knox and Koshkin, {Vadim S.} and Kulkarni, {Amit A.} and Kwon, {Daniel H.} and Sara Matar and McKay, {Rana R.} and Sanjay Mishra and Moria, {Feras A.} and Amanda Nizam and Nock, {Nora L.} and Nonato, {Taylor K.} and Justin Panasci and Lauren Pomerantz and Portuguese, {Andrew J.} and Destie Provenzano and Matthew Puc and Rao, {Yuan J.} and Rhodes, {Terence D.} and Riely, {Gregory J.} and Ripp, {Jacob J.} and Rivera, {Andrea V.} and Erika Ruiz-Garcia and Schmidt, {Andrew L.} and Schoenfeld, {Adam J.} and Schwartz, {Gary K.} and Shah, {Sumit A.} and Justin Shaya and Suki Subbiah and Tachiki, {Lisa M.} and Tucker, {Matthew D.} and Melissa Valdez-Reyes and Weissmann, {Lisa B.} and Wotman, {Michael T.} and Wulff-Burchfield, {Elizabeth M.} and Zhuoer Xie and Yang, {Yuanchu James} and Thompson, {Michael A.} and Shah, {Dimpy P.} and Warner, {Jeremy L.} and Yu Shyr and Choueiri, {Toni K.} and Wise-Draper, {Trisha M.}",

year = "2023",

month = jan,

day = "19",

doi = "10.1001/jamaoncol.2022.5357",

language = "English (US)",

volume = "9",

pages = "128--134",

journal = "JAMA Oncology",

issn = "2374-2437",

publisher = "American Medical Association",

number = "1",

}

TY - JOUR

T1 - Interplay of Immunosuppression and Immunotherapy among Patients with Cancer and COVID-19

AU - Bakouny, Ziad

AU - Labaki, Chris

AU - Grover, Punita

AU - Awosika, Joy

AU - Gulati, Shuchi

AU - Hsu, Chih Yuan

AU - Alimohamed, Saif I.

AU - Bashir, Babar

AU - Berg, Stephanie

AU - Bilen, Mehmet A.

AU - Bowles, Daniel

AU - Castellano, Cecilia

AU - Desai, Aakash

AU - Elkrief, Arielle

AU - Eton, Omar E.

AU - Fecher, Leslie A.

AU - Flora, Daniel

AU - Galsky, Matthew D.

AU - Gatti-Mays, Margaret E.

AU - Gesenhues, Alicia

AU - Glover, Michael J.

AU - Gopalakrishnan, Dharmesh

AU - Gupta, Shilpa

AU - Halfdanarson, Thorvardur R.

AU - Hayes-Lattin, Brandon

AU - Hendawi, Mohamed

AU - Hsu, Emily

AU - Hwang, Clara

AU - Jandarov, Roman

AU - Jani, Chinmay

AU - Johnson, Douglas B.

AU - Joshi, Monika

AU - Khan, Hina

AU - Khan, Shaheer A.

AU - Knox, Natalie

AU - Koshkin, Vadim S.

AU - Kulkarni, Amit A.

AU - Kwon, Daniel H.

AU - Matar, Sara

AU - McKay, Rana R.

AU - Mishra, Sanjay

AU - Moria, Feras A.

AU - Nizam, Amanda

AU - Nock, Nora L.

AU - Nonato, Taylor K.

AU - Panasci, Justin

AU - Pomerantz, Lauren

AU - Portuguese, Andrew J.

AU - Provenzano, Destie

AU - Puc, Matthew

AU - Rao, Yuan J.

AU - Rhodes, Terence D.

AU - Riely, Gregory J.

AU - Ripp, Jacob J.

AU - Rivera, Andrea V.

AU - Ruiz-Garcia, Erika

AU - Schmidt, Andrew L.

AU - Schoenfeld, Adam J.

AU - Schwartz, Gary K.

AU - Shah, Sumit A.

AU - Shaya, Justin

AU - Subbiah, Suki

AU - Tachiki, Lisa M.

AU - Tucker, Matthew D.

AU - Valdez-Reyes, Melissa

AU - Weissmann, Lisa B.

AU - Wotman, Michael T.

AU - Wulff-Burchfield, Elizabeth M.

AU - Xie, Zhuoer

AU - Yang, Yuanchu James

AU - Thompson, Michael A.

AU - Shah, Dimpy P.

AU - Warner, Jeremy L.

AU - Shyr, Yu

AU - Choueiri, Toni K.

AU - Wise-Draper, Trisha M.

PY - 2023/1/19

Y1 - 2023/1/19

N2 - Importance: Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective: To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included 12046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings. Exposures: Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO). Main Outcomes and Measures: The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm. Results: The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79). Conclusions and Relevance: This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm. Trial Registration: ClinicalTrials.gov Identifier: NCT04354701.

AB - Importance: Cytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation. Objective: To determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included 12046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings. Exposures: Immunosuppression due to therapy; systemic anticancer therapy (IO or non-IO). Main Outcomes and Measures: The primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm. Results: The median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79). Conclusions and Relevance: This cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm. Trial Registration: ClinicalTrials.gov Identifier: NCT04354701.

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Interplay of Immunosuppression and Immunotherapy among Patients with Cancer and COVID-19

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