Breakthrough SARS-CoV-2 infections among patients with cancer following two and three doses of COVID-19 mRNA vaccines: a retrospective observational study from the COVID-19 and Cancer Consortium

Toni K Choueiri; Chris Labaki; Ziad Bakouny; Chih-Yuan Hsu; Andrew L Schmidt; Gilberto de Lima Lopes Jr; Clara Hwang; Sunny R K Singh; Chinmay Jani; Lisa B Weissmann; Elizabeth A Griffiths; Susan Halabi; Ulysses Wu; Stephanie Berg; Timothy E O'Connor; Trisha M Wise-Draper; Orestis A Panagiotou; Elizabeth J Klein; Monika Joshi; Fares Yared; Miriam Santos Dutra; Na Tosha N Gatson; Sibel Blau; Harpreet Singh; Rahul Nanchal; Rana R McKay; Taylor K Nonato; Ryann Quinn; Samuel M Rubinstein; Matthew Puc; Blanche H Mavromatis; Praveen Vikas; Bryan Faller; Howard A Zaren; Salvatore Del Prete; Karen Russell; Daniel Y Reuben; Melissa K Accordino; Harpreet Singh; Christopher R Friese; Sanjay Mishra; Donna R Rivera; Yu Shyr; Dimitrios Farmakiotis; Jeremy L Warner

doi:10.1016/j.lana.2023.100445

Breakthrough SARS-CoV-2 infections among patients with cancer following two and three doses of COVID-19 mRNA vaccines: a retrospective observational study from the COVID-19 and Cancer Consortium

Lancet Reg Health Am. 2023 Mar:19:100445. doi: 10.1016/j.lana.2023.100445. Epub 2023 Feb 13.

Authors

Toni K Choueiri¹, Chris Labaki¹, Ziad Bakouny^{1

2}, Chih-Yuan Hsu³, Andrew L Schmidt¹, Gilberto de Lima Lopes Jr⁴, Clara Hwang⁵, Sunny R K Singh⁵, Chinmay Jani⁶, Lisa B Weissmann⁶, Elizabeth A Griffiths⁷, Susan Halabi⁸, Ulysses Wu⁹, Stephanie Berg¹⁰, Timothy E O'Connor¹⁰, Trisha M Wise-Draper¹¹, Orestis A Panagiotou¹², Elizabeth J Klein¹², Monika Joshi¹³, Fares Yared¹⁴, Miriam Santos Dutra¹⁵, Na Tosha N Gatson¹⁶, Sibel Blau¹⁷, Harpreet Singh¹⁸, Rahul Nanchal¹⁸, Rana R McKay¹⁹, Taylor K Nonato¹⁹, Ryann Quinn²⁰, Samuel M Rubinstein²¹, Matthew Puc²², Blanche H Mavromatis²³, Praveen Vikas²⁴, Bryan Faller²⁵, Howard A Zaren²⁶, Salvatore Del Prete²⁷, Karen Russell²⁸, Daniel Y Reuben²⁹, Melissa K Accordino³⁰, Harpreet Singh³¹, Christopher R Friese³², Sanjay Mishra¹², Donna R Rivera³¹, Yu Shyr³, Dimitrios Farmakiotis¹², Jeremy L Warner¹²

Affiliations

¹ Dana-Farber Cancer Institute, Boston, MA, USA.
² Brigham and Women's Hospital, Boston, MA, USA.
³ Department of Biostatistics, Vanderbilt University, Nashville, TN, USA.
⁴ Sylvester Comprehensive Cancer Center at the University of Miami, Miami, FL, USA.
⁵ Division of Hematology and Medical Oncology, Henry Ford Health System, Detroit, MI, USA.
⁶ Department of Internal Medicine, Mount Auburn Hospital, Beth Israel Lahey Health, Cambridge, MA, USA.
⁷ Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
⁸ Duke University Medical Center, Durham, NC, USA.
⁹ Hartford HealthCare Cancer Institute, Hartford, CT, USA.
¹⁰ Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL, USA.
¹¹ University of Cincinnati Cancer Center, Cincinnati, OH, USA.
¹² The Warren Alpert Medical School of Brown University and Lifespan Cancer Institute, Providence, RI, USA.
¹³ Penn State Cancer Institute, Hershey, PA, USA.
¹⁴ Johns Hopkins University, Baltimore, MD, USA.
¹⁵ McGill University Health Centre, Montreal, Quebec, Canada.
¹⁶ Geisinger Health System, Danville, Danville, PA, USA.
¹⁷ Northwest Medical Specialties, PLLC, Puyallup, WA, USA.
¹⁸ Medical College of Wisconsin, Milwaukee, WI, USA.
¹⁹ Moores Cancer Center, University of California San Diego, La Jolla, CA, USA.
²⁰ Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.
²¹ University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
²² Virtua Health, Mt. Holly, NJ, USA.
²³ UPMC Western Maryland, MD, USA.
²⁴ Holden Comprehensive Cancer Center, Iowa City, IA, USA.
²⁵ Missouri Baptist Medical Center Cancer Center/Heartland NCORP, St Louis, MO, USA.
²⁶ St. Joseph's Candler Health System, Savannah, GA, USA.
²⁷ Stamford Hospital, Stamford, CT, USA.
²⁸ Tallahassee Memorial Healthcare, Tallahassee, FL, USA.
²⁹ Medical University of South Carolina, Charleston, SC, USA.
³⁰ Herbert Irving Comprehensive Cancer Center, Vagelos College of Physicians and Surgeons, Columbia University, New York City, NY, USA.
³¹ U.S. Food and Drug Administration, Silver Spring, MD, USA.
³² University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.

Abstract

Background: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines.

Methods: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV).

Findings: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44-0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11-0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45-0.82 and 0.37, 95% CI: 0.24-0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48-0.75 and 0.35, 95% CI: 0.26-0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12-1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06-2.44).

Interpretation: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer.

Funding: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH).

Keywords: Breakthrough infection; Cancer; Covid-19; SARS-CoV-2; Vaccination; mRNA vaccine.

Abstract

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