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. 2023 Jan 1;9(1):128-134.
doi: 10.1001/jamaoncol.2022.5357.

Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19

Ziad Bakouny  1 , Chris Labaki  1 , Punita Grover  2 , Joy Awosika  2 , Shuchi Gulati  2 , Chih-Yuan Hsu  3 , Saif I Alimohamed  4 , Babar Bashir  5 , Stephanie Berg  6 , Mehmet A Bilen  7 , Daniel Bowles  8 , Cecilia Castellano  7 , Aakash Desai  9 , Arielle Elkrief  9 , Omar E Eton  10 , Leslie A Fecher  11 , Daniel Flora  12 , Matthew D Galsky  13 , Margaret E Gatti-Mays  14 , Alicia Gesenhues  12 , Michael J Glover  15 , Dharmesh Gopalakrishnan  16 , Shilpa Gupta  17 , Thorvardur R Halfdanarson  9 , Brandon Hayes-Lattin  18 , Mohamed Hendawi  19 , Emily Hsu  10 , Clara Hwang  20 , Roman Jandarov  2 , Chinmay Jani  21 , Douglas B Johnson  3 , Monika Joshi  22 , Hina Khan  23 , Shaheer A Khan  24 , Natalie Knox  6 , Vadim S Koshkin  25 , Amit A Kulkarni  26 , Daniel H Kwon  25 , Sara Matar  27 , Rana R McKay  28 , Sanjay Mishra  3 , Feras A Moria  29 , Amanda Nizam  17 , Nora L Nock  30 , Taylor K Nonato  28 , Justin Panasci  31 , Lauren Pomerantz  22 , Andrew J Portuguese  32 , Destie Provenzano  33 , Matthew Puc  34 , Yuan J Rao  33 , Terence D Rhodes  35 , Gregory J Riely  36 , Jacob J Ripp  37 , Andrea V Rivera  5 , Erika Ruiz-Garcia  38 , Andrew L Schmidt  1 , Adam J Schoenfeld  36 , Gary K Schwartz  24 , Sumit A Shah  15 , Justin Shaya  28 , Suki Subbiah  39 , Lisa M Tachiki  32 , Matthew D Tucker  3 , Melissa Valdez-Reyes  38 , Lisa B Weissmann  21 , Michael T Wotman  13 , Elizabeth M Wulff-Burchfield  37 , Zhuoer Xie  9 , Yuanchu James Yang  3 , Michael A Thompson  19   40 , Dimpy P Shah  41 , Jeremy L Warner  3 , Yu Shyr  3 , Toni K Choueiri  1 , Trisha M Wise-Draper  2 ; COVID-19 and Cancer Consortium
Collaborators, Affiliations

Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19

Ziad Bakouny et al. JAMA Oncol. .

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 12 046 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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Bakouny reported nonfinancial support from Bristol Myers Squibb, grants from Genentech/imCORE, and personal fees from UpToDate outside the submitted work. Dr Labaki reported grants from Genentech/imCORE outside the submitted work. Dr Gulati reported support to institution for a clinical trial from AstraZenca and Isoray, and personal fees from EMD Serono for advisory board roles outside the submitted work. Dr Bashir reported research funding to institution from Amgen, Artios Pharmaceuticals Bicycle Therapeutics, Boehringer Ingelheim, Daiichi Snakyo, KAHR, Merck, Pionyr Immunotherapeutics, RASCAL Therapeutics, Syros Pharmaceuticals,and Tarveda Therapeutics. Dr Berg reported speakers bureau fees from Eisai, Exelexis, and Bristol Meyers Squibb outside the submitted work. Dr Bilen reported personal fees from Exelixis, Bayer, BMS, Eisai, Pfizer, AstraZeneca, Janssen, Calithera Biosciences, Genomic Health, Nektar, EMD Serono, SeaGen, and Sanofi; advisory board and grants from Merck, Xencor, Bayer, Bristol Myers Squibb, Genentech/Roche, SeaGen, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Genome & Company, AAA, Peloton Therapeutics, and a grant to institution from Pfizer outside the submitted work. Dr Elkrief reported grants from the Canadian Institute of Health Research outside the submitted work. Dr Eton reported grants from BMS outside the submitted work. Dr Fecher reported grants for clinical trial funding to institution from BMS, Kartos, Array-Pfizer, and EMD/Serono-Pfizer; personal fees from Elsevier, study funding from Array-Pfizer ECOG-ACRIN, and funding grants to institution from Merck-Incyte outside the submitted work. Dr Galsky reported personal fees from BMS, Merck, Genentech, AstraZeneca, Pfizer, EMD Serono, SeaGen, Janssen, NuMab, Dragonfly, Glaxo Smith Kline, Basliea, Urogen, Rappta Therapeutics, Alligator, and Dracen outside the submitted work. Dr Gatti-Mays reported institutional research support from Regeneron outside the submitted work. Dr Gupta reported personal fees and/or consulting fees from Merck, EMD Sorono, Pfizer, BMS, Janssen, Bayer, Gilead, Seattle Genetics, Natera, and Loxo Oncology, outside the submitted work. Dr Halfdanarson reported grants, consulting fees and/or research support to institution from Advanced Accelerator Applications, Thermo Fisher Scientific, Turnstone Biologics, Basilea, Ipsen, ITM Isotopen Technologien Muenchen, TerSera, Curium, and Terumo, outside the submitted work. Dr Hwang reported grants to institution from Merck, Bayer, Genentech, AstraZeneca, and Bausch Health outside the submitted work; fees received from TEMPUS, Genzyme, EMD Sorono for consulting; stock holdings in Johnson & Johnson; and speaker fees from OncLive. Dr Johnson reported advising/consulting fees from BMS, Catalyst, Iovance, Jansen, Mallinckrodt, Merck, Mosaic, Novartis, Oncosec, Pfizer, and Targovax outside the submitted work; in addition, Dr Johnson had a patent for MHC-II as biomarker of immune therapy issued. Dr Joshi reported grants to Institution from AstraZeneca, Pfizer, Eisai, and Seagen outside the submitted work. Dr Kulkarni reported grants from AstraZeneca and personal and advisory board fees from Genentech outside the submitted work. Dr McKay reported research funding from Bayer, Pfizer, Tempus; serves on Advisory Board/consultant for AstraZenca, Aveo, Bayer, Bristol Myers Squib, Calithera, Caris, Dendreon, Exelixis, Janssen, Merck, Myovant, Novartis, Pfizer, Sanofi, Sorrento Therapeutics, and Tempus. Dr Mishra reported grants from National Cancer Institute Support through institution from grant [Grant P30 CA068485], grants from International Association for the Study of Lung Cancer Support through institution, and funding from American Association for Cancer Research Support through institution during the conduct of the study; personal fees from National Geographic for writing articles outside the submitted work. Dr Portuguese reported grants from National Heart, Lung, and Blood Institute (T32 HL007093) during the conduct of the study. Dr Rhodes reported personal fees from BMS, Merck, and AstraZeneca outside the submitted work. Dr Riely reported grants to institution from Pfizer, Novartis, Takeda, Roche, Mirati, and Merck outside the submitted work. Dr Ruiz-Garcia reported personal fees from ROCHE/Genentech, Amgen, Merck, BMS, and Bayer outside the submitted work. Dr Schoenfeld reported personal fees from J&J, KSQ therapeutics, BMS, Enara Bio, and Heat Biologics; research funding paid to institution from GSK , PACT Pharma, Iovance Biotherapeutics, Achilles therapeutics, Merck Research, BMS, and Harpoon; and personal fees from Perceptive advisors outside the submitted work. Dr Tachiki reported grants from the National Institutes of Health (NIH T32CA009515-37) during the conduct of the study. Dr Wulff-Burchfield reported grants from Pfizer global medical grants, personal fees, advisory board, or consulting fees from Astellas Consulting, personal fees from Aveo Oncology, Bristol Myers Squibb, Exelixis, and Janssen, a family member with stock ownership in Immunomedics and Nektar outside the submitted work. Dr Thompson reported employment from Tempus Labs and Doximity; stock, personal fees from Takeda; royalties, advisory board, and/or personal fees from UpToDate, Adaptive, AbbVie, Elsevier Clinical Path, Epizyme, Janssen, Sanofi, Syapse, and GRAIL/Illumina outside the submitted work. Dr D. Shah reported grants from The American Cancer Society and Hope Foundation for Cancer Research (MRSG-16-152-01-CCE) and grants from NIH (P30CA054174) during the conduct of the study. Dr Warner reported grants from NIH during the conduct of the study; grants from AACR and Vanderbilt University; personal fees from Westat, Melax Tech, Roche, and Flatiron Health; and ownership of HemOnc.org LLC outside the submitted work. Dr Shyr reported grants from NIH/NCI during the conduct of the study; grants from NIH outside the submitted work. Dr Choueiri reported unpaid memberships from CCC19 SC and ESMO-CoCare member during the conduct of the study; and advisory boards and consultancy regarding drug developments in GU cancers from Pfizer, Merck, BMS, Exelixis, EMD Serono, Roche, Aveo, J&J, and others. Dr Wise-Draper reported grants for clinical trial grant support from BMS, Merck & Co, Janssen, AstraZeneca, and Tesaro/GSK; and personal fees from Caris Life Sciences. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Forest Plot of Adjusted Odds Ratios for COVID-19 Severity, Stratified by Immunosuppression Status
aOR indicates adjusted odds ratio; ECOG PS, Eastern Cooperative Oncology Group performance score; IO, immunotherapy.
Figure 2.
Figure 2.. Forest Plot of Adjusted Odds Ratios for Cytokine Storm, Stratified by Immunosuppression Status
aOR indicates adjusted odds ratio; ECOG PS, Eastern Cooperative Oncology Group performance score; IO, immunotherapy.
See this image and copyright information in PMC

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