Systemic Anticancer Therapy and Thromboembolic Outcomes in Hospitalized Patients With Cancer and COVID-19
Authors: Gulati Shuchi , Hsu Chih-Yuan , Shah Surbhi , Shah Pankil K. , Zon Rebecca , Alsamarai Susan , Awosika Joy , El-Bakouny Ziad , Bashir Babar , Beeghly Alicia , Berg Stephanie , de-la-Rosa-Martinez Daniel , Doroshow Deborah B. , Egan Pamela C. , Fein Joshua , Flora Daniel B. , Friese Christopher R. , Fromowitz Ariel , Griffiths Elizabeth A. , Hwang Clara , Jani Chinmay , Joshi Monika , Khan Hina , Klein Elizabeth J. , Heater Natalie Knox , Koshkin Vadim S. , Kwon Daniel H. , Labaki Chris , Latif Tahir , McKay Rana R. , Nagaraj Gayathri , Nakasone Elizabeth S. , Nonato Taylor , Polimera Hyma V. , Puc Matthew , Razavi Pedram , Ruiz-Garcia Erika , Saliby Renee Maria , Shastri Aditi , Singh Sunny R. K. , Tagalakis Vicky , Vilar-Compte Diana , Weissmann Lisa B. , Wilkins Cy R. , Wise-Draper Trisha M. , Wotman Michael T. , Yoon James J. , Mishra Sanjay , Grivas Petros , Shyr Yu , Warner Jeremy L. , Connors Jean M. , Shah Dimpy P. , Rosovsky Rachel P. ,   COVID-19 and Cancer Consortium, Gandhi Rikin , Gartrell Benjamin A. , Goel Sanjay , Halmos Balazs , Makower Della F. , O' Sullivan Darciann , Ohri Nitin , Sica R. Alejandro , Verma Amit K. , Butt Omar , 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 , Thompson Michael A. , Lammers Philip E. , Loree Jonathan M. , Yu Irene S. , Bindal Poorva , Lam Barbara , Peters Mary Linton B. , Piper-Vallillo Andrew J. , Arvanitis Panos , Egan Pamela C. , Farmakiotis Dimitrios , 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 , Gupta Shilpa , Nizam Amanda , Pennell Nathan A. , Sharifi Nima , Hoppenot Claire , Li Ang , Bitterman Danielle S. , Choueiri Toni K. , Connors Jean M. , Demetri George D. , El Zarif Talal , Florez Narjust , Freeman Dory A. , Giordano Antonio , Morgans Alicia K. , Nohria Anju , Tolaney Sara M. , Van Allen Eliezer M. , Xu Wenxin Vincent , Halabi Susan , Zhang Tian , Dzimitrowicz Hannah , Leighton John C. , Graber Jerome J. , Hawley Jessica E. , Loggers Elizabeth T. , Lyman Gary H. , Lynch Ryan C. , Portuguese Andrew J. , Schweizer Michael T. , Su Christopher T. , Tachiki Lisa , Vinayak Shaveta , Wagner Michael J. , Yeh Albert , Dansoa Yvonne , Gatson Na Tosha N. , Makary Mina , Manikowski Jesse J. , Vadakara Joseph , Yossef Kristena , Beckerman Jennifer , Goyal Sharad , Messing Ian , Provenzano Destie , Rao Yuan James , Rosenstein Lori J. , Steffes Dawn R. , Clement Jessica M. , Cosin Jonathan A. , Daher Ahmad , Dailey Mark E. , Elias Rawad , Eton Omar E. , Hosmer Wylie , Hsu Emily , Jayaraj Asha , Mather Jeff , Menendez Alvaro G. , Nadkarni Rajani , Serrano Oscar K. , Yu Peter Paul , Gadgeel Shirish M. , Tejwani Sheela , Accordino Melissa K. , Bhutani Divaya , Bodin Brianne E. , Hershman Dawn L. , Ingham Matthew , Khan Shaheer A. , Masson Cynthia , Schwartz Gary K. , Alexander Mariam , Matar Sara , Reuben Daniel Y. , Bernicker Eric H. , Deeken John F. , Jeffords Kelly J. , Shafer Danielle , Cárdenas-Delgado Ana I. , Cuervo Campos Rogelio , De-la-Rosa-Martinez Daniel , Ramirez Ana , Valdez-Reyes Nadia Melissa , Gill David M. , Lewis Mark A. , Low Clarke A. , Rhodes Terence D. , Jones Michelle M. , Mansoor Abdul-Hai , Mashru Sandeep H. , Werner Mica A. , Cohen Aaron M. , Hayes-Lattin Brandon M. , McWeeney Shannon , Nemecek Eneida R. , Williamson Staci P. , Lewis Grant C. , Smith Stephanie J. , Akhtari Mojtaba , Castillo Dan R. , Cortez Kimberly , Park Kyu , Reeves Mark E. , Berg Stephanie , O'Connor Timothy E. , Altman Jessica , Gurley Michael , Mulcahy Mary F. , Wehbe Firas H. , Durbin Eric B. , Kulkarni Amit A. , Nelson Heather H. , Ramesh Vidhyalakshmi , Sachs Zohar , Wilson Grace , Bardia Aditya , Boland Genevieve , Gainor Justin F. , Peppercorn Jeffrey , Reynolds Kerry L. , Zubiri Leyre , Campian Jian Li , Smith Katherine E. , Bekaii-Saab Tanios S. , Desai Aakash , Halfdanarson Thorvardur R. , Joyner Michael J. , Riaz Irbaz B. , Senefeld Jonathon W. , Williams Colt , Bonnen Mark , Mahadevan Daruka , Ramirez Amelie G. , Salazar Mary , Wang Chen-Pin , Mesa Ruben A. , Bouganim Nathaniel , Elkrief Arielle , Moria Feras , Panasci Justin , Papenburg Jesse , Vinh Donald C. , Nanchal Rahul , Singh Harpreet , Bahadur Nadia , Bao Ting , Nambiar Puja H. , O’Cearbhaill Roisin E. , Papadopoulos Esperanza B. , Philip John , Riely Gregory J. , Robson Mark , Rosenberg Jonathan E. , Schoenfeld Adam J. , Tamimi Rulla , Cerrone Kim , Dill Jennifer , Faller Bryan A. , Ajmera Archana , Brouha Sharon S. , Choi Sharon , Hsiao Albert , 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 , Namburi Swathi , Pomerantz Lauren D. , Rovito Marc A. , Advani Pragati E. , Cronin Tara , Fleissner Bridget , Goel Shipra , Gopalakrishnan Dharmesh , Hernandez-Ilizaliturri Francisco , Jain Prantesh , Kariapper Ariffa , Levine Ellis , Moffitt Melissa , O'Connor Tracey L. , Puzanov Igor , Smith Laurie J. , Wicher Camille P. , Zsiros Emese , Jabbour Salma K. , Misdary Christian F. , Shah Mansi R. , Batist Gerald , Cook Erin , Esfahani Khashayar , Ferrario Cristiano , Lau Susie , Ma Kim , Miller Wilson H. , Rudski Lawrence , Santos Dutra Miriam , Wilchesky Machelle , Mahmood Sana Z. , McNair Christopher , Mico Vasil , Rivera Andrea Verghese , Dixon Becky , Heilman Hannah , Logan Barbara B. , Mandapakala Chaitanya , Cabebe Elwyn C. , Glover Michael J. , Jha Alokkumar , Khaki Ali Raza , Nagpal Seema , Schapira Lidia , Shah Sumit A. , Wu Julie Tsu-Yu , Subbiah Suki , 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. , Gatti-Mays Margaret E. , Jhawar Sachin R. , Palmer Joshua D. , Pillainayagam Clement , Stover Daniel G. , Wall Sarah , Williams Nicole O. , Abbasi Saqib Hussen , Annis Sandy , Greenland Steven , Jones Regina , Kasi Anup , Rock Crosby D. , Wulff-Burchfield Elizabeth M. , Smits Melissa , Weiss Matthias , Chism David D. , Owenby Susie , Ang Celina , Galsky Matthew D. , Metzger Megan , Berenberg Jeffrey , Uyehara Catherine , Fazio Alyson , Huber Kathryn E. , Lashley Latoya N. , Sueyoshi Mark H. , Patel Kanishka G. , Riess Jonathan W. , Borno Hala T. , Small Eric J. , Zhang Sylvia , Andermann Tessa M. , Jensen Christopher E. , Rubinstein Samuel M. , Wood William A. , Ahmad Syed A. , Grover Punita , Jandarov Roman , Kharofa Jordan , Li Ningjing , Marcum Michelle , Sohal Davendra P. S. , Zamulko Olga , Abidi Maheen , Balmaceda Nicole B. , Bowles Daniel W. , 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 , Boldt Anne M. , Fecher Leslie A. , Su Chris , Bijjula Ragneel , Mavromatis Blanche H. , Seletyn Mildred E. , Wood Barbara R. , Zaman Qamar U. , Kaklamani Virginia , 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 , Johnson Douglas B. , Lewis Judy T. , Li Xuanyi (Lexi) , Prescott Lauren S. , Reid Sonya A. , Saif Sara , Shyr Yu , Slosky David A. , Solorzano Carmen C. , Sun Tianyi , Wang Lucy L. , Yang Yuanchu James , Aboulafia David M. , Carducci Theresa M. , Goldsmith Karen J. , Van Loon Susan , Topaloglu Umit , Moore Joan , Cabalona Wilhelmina D. , Shisler Elizabeth , Barrow McCollough Briana , Peddi Prakash , Rosen Lane R. , Bilen Mehmet A. , Castellano Cecilia A. , Ravindranathan Deepak , Hafez Navid , Herbst Roy S. , LoRusso Patricia , Lustberg Maryam B. , Masters Tyler , Stratton Catherine , Painter Corrie A. , Peters Solange 
Published: August 2023

Importance

Systematic data on the association between anticancer therapies and thromboembolic events (TEEs) in patients with COVID-19 are lacking.

Objective

To assess the association between anticancer therapy exposure within 3 months prior to COVID-19 and TEEs following COVID-19 diagnosis in patients with cancer.

Design, Setting, and Participants

This registry-based retrospective cohort study included patients who were hospitalized and had active cancer and laboratory-confirmed SARS-CoV-2 infection. Data were accrued from March 2020 to December 2021 and analyzed from December 2021 to October 2022.

Exposure

Treatments of interest (TOIs) (endocrine therapy, vascular endothelial growth factor inhibitors/tyrosine kinase inhibitors [VEGFis/TKIs], immunomodulators [IMiDs], immune checkpoint inhibitors [ICIs], chemotherapy) vs reference (no systemic therapy) in 3 months prior to COVID-19.

Main Outcomes and Measures

Main outcomes were (1) venous thromboembolism (VTE) and (2) arterial thromboembolism (ATE). Secondary outcome was severity of COVID-19 (rates of intensive care unit admission, mechanical ventilation, 30-day all-cause mortality following TEEs in TOI vs reference group) at 30-day follow-up.

Results

Of 4988 hospitalized patients with cancer (median [IQR] age, 69 [59-78] years; 2608 [52%] male), 1869 had received 1 or more TOIs. Incidence of VTE was higher in all TOI groups: endocrine therapy, 7%; VEGFis/TKIs, 10%; IMiDs, 8%; ICIs, 12%; and chemotherapy, 10%, compared with patients not receiving systemic therapies (6%). In multivariable log-binomial regression analyses, relative risk of VTE (adjusted risk ratio [aRR], 1.33; 95% CI, 1.04-1.69) but not ATE (aRR, 0.81; 95% CI, 0.56-1.16) was significantly higher in those exposed to all TOIs pooled together vs those with no exposure. Among individual drugs, ICIs were significantly associated with VTE (aRR, 1.45; 95% CI, 1.01-2.07). Also noted were significant associations between VTE and active and progressing cancer (aRR, 1.43; 95% CI, 1.01-2.03), history of VTE (aRR, 3.10; 95% CI, 2.38-4.04), and high-risk site of cancer (aRR, 1.42; 95% CI, 1.14-1.75). Black patients had a higher risk of TEEs (aRR, 1.24; 95% CI, 1.03-1.50) than White patients. Patients with TEEs had high intensive care unit admission (46%) and mechanical ventilation (31%) rates. Relative risk of death in patients with TEEs was higher in those exposed to TOIs vs not (aRR, 1.12; 95% CI, 0.91-1.38) and was significantly associated with poor performance status (aRR, 1.77; 95% CI, 1.30-2.40) and active/progressing cancer (aRR, 1.55; 95% CI, 1.13-2.13).

Conclusions and Relevance

In this cohort study, relative risk of developing VTE was high among patients receiving TOIs and varied by the type of therapy, underlying risk factors, and demographics, such as race and ethnicity. These findings highlight the need for close monitoring and perhaps personalized thromboprophylaxis to prevent morbidity and mortality associated with COVID-19–related thromboembolism in patients with cancer.