Background Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of anti-neoplastic systemic therapies can result in less robust antibody titres following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. Patients and methods We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes to those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; ClinicalTrials.gov number, NCT04354701). Results Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. Conclusions Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. However, patients with cancer who develop breakthrough infection despite full vaccination remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

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