Interplay of Immunosuppression and Immunotherapy Among Patients With Cancer and COVID-19
Authors: Bakouny Ziad , Labaki Chris , Grover Punita , Awosika Joy , Gulati Shuchi , Hsu Chih-Yuan , Alimohamed Saif I. , Bashir Babar , Berg Stephanie , Bilen Mehmet A. , Bowles Daniel , Castellano Cecilia , Desai Aakash , Elkrief Arielle , Eton Omar E. , Fecher Leslie A. , Flora Daniel , Galsky Matthew D. , Gatti-Mays Margaret E. , Gesenhues Alicia , Glover Michael J. , Gopalakrishnan Dharmesh , Gupta Shilpa , Halfdanarson Thorvardur R. , Hayes-Lattin Brandon , Hendawi Mohamed , Hsu Emily , Hwang Clara , Jandarov Roman , Jani Chinmay , Johnson Douglas B. , Joshi Monika , Khan Hina , Khan Shaheer A. , Knox Natalie , Koshkin Vadim S. , Kulkarni Amit A. , Kwon Daniel H. , Matar Sara , McKay Rana R. , Mishra Sanjay , Moria Feras A. , Nizam Amanda , Nock Nora L. , Nonato Taylor K. , Panasci Justin , Pomerantz Lauren , Portuguese Andrew J. , Provenzano Destie , Puc Matthew , Rao Yuan J. , Rhodes Terence D. , Riely Gregory J. , Ripp Jacob J. , Rivera Andrea V. , Ruiz-Garcia Erika , Schmidt Andrew L. , Schoenfeld Adam J. , Schwartz Gary K. , Shah Sumit A. , Shaya Justin , Subbiah Suki , Tachiki Lisa M. , Tucker Matthew D. , Valdez-Reyes Melissa , Weissmann Lisa B. , Wotman Michael T. , Wulff-Burchfield Elizabeth M. , Xie Zhuoer , Yang Yuanchu James , Thompson Michael A. , Shah Dimpy P. , Warner Jeremy L. , Shyr Yu , Choueiri Toni K. , Wise-Draper Trisha M. ,   COVID-19 and Cancer Consortium, Fromowitz Ariel , Gandhi Rikin , Gartrell Benjamin A , Goel Sanjay , Halmos Balazs , Makower Della F , O' Sullivan Darciann , Ohri Nitin , Portes Mary , Shapiro Lauren C , Shastri Aditi , Sica R Alejandro , Verma Amit K , Butt Omar , Campian Jian Li , Fiala Mark A , Henderson Jeffrey P , Monahan Ryan S , Stockerl-Goldstein Keith E , Zhou Alice Y , Bitran Jacob D , Hallmeyer Sigrun , Mundt Daniel , Pandravada Sasirekha , Papaioannou Philip V , Patel Mauli , Streckfuss Mitrianna , Tadesse Eyob , Gatson Na Tosha N , Kundranda Madappa N , Lammers Philip E , Loree Jonathan M , Yu Irene S , Bindal Poorva , Lam Barbara , Peters Mary Linton B , Piper-Vallillo Andrew J , Egan Pamela C , Farmakiotis Dimitrios , Arvanitis Panos , Klein Elizabeth J , Olszewski Adam J , Vieira Kendra , Angevine Anne H , Bar Michael H , Del Prete Salvatore A , Fiebach Maryann Z , Gulati Anthony P , Hatton Edward , Houston Kaly , Rose Suzanne J , Steve Lo K M , Stratton Jamie , Weinstein Paul L , Garcia Jorge A , Routy Bertrand , Hoyo-Ulloa Irma , Dawsey Scott J , Lemmon Christopher A , Pennell Nathan A , Sharifi Nima , Painter Corrie A , Granada Carolina , Hoppenot Claire , Li Ang , Bitterman Danielle S , Connors Jean M , Demetri George D , Florez (Duma) Narjust , Freeman Dory A , Giordano Antonio , Morgans Alicia K , Nohria Anju , Saliby Renee Maria , Tolaney Sara M , Van Allen Eliezer M , Xu Wenxin Vincent , Zon Rebecca L , Halabi Susan , Zhang Tian , Dzimitrowicz Hannah , Leighton John C , Graber Jerome J , Grivas Petros , Hawley Jessica E , Loggers Elizabeth T , Lyman Gary H , Lynch Ryan C , Nakasone Elizabeth S , Schweizer Michael T , Vinayak Shaveta , Wagner Michael J , Yeh Albert , Dansoa Yvonne , Makary Mina , Manikowski Jesse J , Vadakara Joseph , Yossef Kristena , Beckerman Jennifer , Goyal Sharad , Messing Ian , Rosenstein Lori J , Steffes Dawn R , Alsamarai Susan , Clement Jessica M , Cosin Jonathan A , Daher Ahmad , Dailey Mark E , Elias Rawad , Fein Joshua A , Hosmer Wylie , Jayaraj Asha , Mather Jeff , Menendez Alvaro G , Nadkarni Rajani , Serrano Oscar K , Yu Peter Paul , Balanchivadze Nino , Gadgeel Shirish M , Accordino Melissa K , Bhutani Divaya , Bodin Brianne E , Hershman Dawn L , Masson Cynthia , Alexander Mariam , Mushtaq Sarah , Reuben Daniel Y , Bernicker Eric H , Deeken John F , Jeffords Kelly J , Shafer Danielle , Cárdenas Ana I , Cuervo Campos Rogelio , De-la-Rosa-Martinez Daniel , Ramirez Ana , Vilar-Compte Diana , Gill David M , Lewis Mark A , Low Clarke A , Jones Michelle M , Mansoor Abdul-Hai , Mashru Sandeep H , Werner Mica A , Cohen Aaron M , McWeeney Shannon , Nemecek Eneida R , Williamson Staci P , Peters Solange , Smith Stephanie J , Lewis Grant C , Zaren Howard A , Akhtari Mojtaba , Castillo Dan R , Cortez Kimberly , Lau Eric , Nagaraj Gayathri , Park Kyu , Reeves Mark E , O'Connor Timothy E , Altman Jessica , Gurley Michael , Mulcahy Mary F , Wehbe Firas H , Durbin Eric B , Nelson Heather H , Ramesh Vidhyalakshmi , Sachs Zohar , Wilson Grace , Bardia Aditya , Boland Genevieve , Gainor Justin F , Peppercorn Jeffrey , Reynolds Kerry L , Rosovsky Rachel P , Zubiri Leyre , Bekaii-Saab Tanios S , Joyner Michael J , Riaz Irbaz B , Senefeld Jonathon  W , Shah Surbhi , Ayre Susan K , Bonnen Mark , Mahadevan Daruka , McKeown Cindy , Mesa Ruben A , Ramirez Amelie G , Salazar Mary , Shah Pankil K , Wang Chen-Pin , Bouganim Nathaniel , Papenburg Jesse , Sabbah Arielle , Tagalakis Vicky , Vinh Donald C , Nanchal Rahul , Singh Harpreet , Bahadur Nadia , Bao Ting , Belenkaya Rimma , Nambiar Puja  H , O’Cearbhaill Roisin E , Papadopoulos Esperanza B , Philip John , Robson Mark , Rosenberg Jonathan E , Wilkins Cy R , Tamimi Rulla , Cerrone Kim , Dill Jennifer , Faller Bryan A , Alomar Mohammed E , Chandrasekhar Sanjay A , Hume Emma C , Islam Jessica Y , Ajmera Archana , Brouha Sharon S , Cabal Angelo , Choi Sharon , Hsiao Albert , Jiang Jun Yang , Kligerman Seth , Park Ji , Razavi Pedram , Reid Erin G , Bhatt Padmanabh S , Mariano Melissa G , Thomson Carey C , Glace Mary (Grace) , Knoble Jeanna L , Rink Cameron , Zacks Rosemary , Blau Sibel H , Brown CarrieAnn , Cantrell Angela Shaw , Namburi Swathi , Polimera Hyma V , Rovito Marc A , Edwin Natasha , Herz Katrina , Kennecke Hagen F , Monfared Amelia , Sautter Rachel R , Cronin Tara , Elshoury Amro , Fleissner Bridget , Griffiths Elizabeth A , Hernandez-Ilizaliturri Francisco , Jain Prantesh , Kariapper Ariffa , Levine Ellis , Moffitt Melissa , O'Connor Tracey L , Smith Laurie J , Wicher Camille P , Zsiros Emese , Jabbour Salma K , Misdary Christian F , Shah Mansi R , Batist Gerald , Cook Erin , Ferrario Cristiano , Lau Susie , Miller Wilson  H , Rudski Lawrence , Santos Dutra Miriam , Wilchesky Machelle , Mahmood Sana Z , McNair Christopher , Mico Vasil , Dixon Becky , Kloecker Goetz , Logan Barbara B , Mandapakala Chaitanya , Cabebe Elwyn C , Jha Alokkumar , Khaki Ali Raza , Nagpal Seema , Schapira Lidia , Wu Julie Tsu-Yu , Whaley David , Lopes Gilberto de Lima , de Cardenas Karen , Russell Karen , Stith Brittany , Taylor Sharona , Klamerus Justin F , Revankar Sanjay G , Addison Daniel , Chen James L , Haynam Marcy , Jhawar Sachin R , Karivedu Vidhya , Palmer Joshua D , Pillainayagam Clement , Stover Daniel G , Wall Sarah , Williams Nicole O , Abbasi Saqib Hussen , Annis Sandy , Balmaceda Nicole B , Greenland Steven , Kasi Anup , Rock Crosby D , Luders Matt , Smits Melissa , Weiss Matthias , Chism David D , Owenby Susie , Ang Celina , Doroshow Deborah B , Metzger Megan , Berenberg Jeffrey , Uyehara Catherine , Fazio Alyson , Huber Kathryn E , Lashley Latoya N , Sueyoshi Mark H , Patel Kanishka G , Riess Jonathan , Borno Hala T , Small Eric J , Zhang Sylvia , Andermann Tessa M , Jensen Christopher  E , Rubinstein Samuel M , Wood William A , Ahmad Syed A , Brownfield Lauren , Heilman Hannah , Kharofa Jordan , Latif Tahir , Marcum Michelle , Shaikh Hira  G , Sohal Davendra P S , Abidi Maheen , Geiger Christopher L , Markham Merry-Jennifer , Russ Atlantis  D , Saker Haneen , Acoba Jared D , Choi Horyun , Rho Young Soo , Feldman Lawrence E , Gantt Gerald , Hoskins Kent F , Khan Mahir , Liu Li C , Nguyen Ryan H , Pasquinelli Mary M , Schwartz Candice , Venepalli Neeta K , Vikas Praveen , Zakharia Yousef , Friese Christopher R , Boldt Anne , Gonzalez Cyndi J , Su Chris , Su Christopher T , Yoon James J , Bijjula Ragneel , Mavromatis Blanche H , Seletyn Mildred E , Wood Barbara R , Zaman Qamar U , Kaklamani Virginia , Beeghly Alicia , Brown Alaina J , Charles Lawrence J , Cheng Alex , Crispens Marta A , Croessmann Sarah , Davis Elizabeth J , Ding Tan , Duda Stephany N , Enriquez Kyle T , French Benjamin , Gillaspie Erin A , Hausrath Daniel J , Hennessy Cassandra , Lewis Judy T , Li Xuanyi (Lexi) , Prescott Lauren S , Reid Sonya A , Saif Sara , Slosky David A , Solorzano Carmen C , Sun Tianyi , Vega-Luna Karen , Wang Lucy L , Aboulafia David M , Carducci Theresa M , Goldsmith Karen J , Van Loon Susan , Topaloglu Umit , Moore Joan , Rice Robert L , Cabalona Wilhelmina D , Cyr Sandra , Barrow McCollough Briana , Peddi Prakash , Rosen Lane R , Ravindranathan Deepak , Hafez Navid , Herbst Roy S , LoRusso Patricia , Lustberg Maryam B , Masters Tyler , Stratton Catherine 
Published: November 2022

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