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, 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 YaredMiriam 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, Christopher R. Friese, Sanjay Mishra, Donna R. Rivera, Yu Shyr, Dimitrios Farmakiotis, Jeremy L. Warner

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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 yP30 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).

Original languageEnglish (US)
Article number100445
JournalThe Lancet Regional Health - Americas
StatePublished - Mar 2023

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Health Policy
  • Public Health, Environmental and Occupational Health

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