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Master of Public Health

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

AUTHORS

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 , , . JAMA oncology. 2022 11 3; ().

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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