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Severe outcomes in vaccinated cancer patients with breakthrough COVID

The first study to evaluate the clinical characteristics and outcomes of fully vaccinated patients with cancer who had breakthrough COVID-19 infections indicates they remained at high risk for hospitalisation and death, found a study in Annals of Oncology.

It showed that fully vaccinated patients who experienced breakthrough infections had a hospitalisation rate of 65%, an ICU or mechanical ventilation rate of 19%, and a 13% death rate. The study was conducted by the COVID-19 and Cancer Consortium (CCC19), a group of 129 research centres that has been tracking the impact of COVID-19 on patients with cancer since the beginning of the pandemic.

“Patients with cancer who develop breakthrough COVID-19 even after full vaccination can still experience severe outcomes, including death,” said Dr Toni Choueiri, director of the Lank Center for Genitourinary Care at Dana-Farber Cancer Institute and a senior author on the report. “That is why a multilayered approach that includes masking and social-distancing, along with vaccination plus booster against COVID-19, remains an essential approach for the foreseeable future.”

Patients were considered fully vaccinated after having received two doses of either the BioNTech, Pfizer, or the Moderna, NIAD vaccine, or one dose of the J&J vaccine, with the last vaccine dose long enough before breakthrough COVID-19, to consider them as fully vaccinated. The data were collected between 1 November 2020 and 31 May 2021, before booster vaccines were recommended for patients with cancer by the US Centers for Disease Control and Prevention.

“Because measures of immunity are not routinely collected in clinical care, we don’t know whether these were patients who mounted effective immune responses after vaccination; a lot of emerging data have suggested that patients with cancer, especially blood cancers, don’t mount adequate protective antibody responses. It’s important to note that many of the same factors that we identified prior to the availability of vaccination, like age, comorbidities, performance status, and progressing cancer, still seem to drive many of the bad outcomes,” said Dr Jeremy Warner, director of the CCC19 Research Coordinating Center, associate professor at Vanderbilt-Ingram Cancer Center and a senior author of the study.

The consortium identified 1,787 patients with cancer and COVID-19 for the study, the vast majority of whom were unvaccinated. The number of fully vaccinated was 54, and 46% of those fully vaccinated had reduced levels of lymphocytes, the T cells and B cells responsible for immunological responses to viruses. Lymphopenia commonly occurs in patients with cancer receiving anti-CD20 monoclonal antibodies or CAR-T-cell treatments for haematologic malignancies, including lymphoma and leukaemia.

The study appears to support previous observations that patients with haematologic malignancies are at greater risk for severe outcomes from COVID-19. However, the number of patients in the study is too small to make definitive conclusions about specific types of anticancer therapies that might be associated with breakthrough infections, the researchers noted. Patients on a treatment regimen of corticosteroids also appeared to be more susceptible to hospitalisation.

“Similar results (high mortality rates among fully vaccinated individuals) have been reported in other immunocompromised patient populations, such as organ transplant recipients, before the use of additional vaccine doses. These findings come at a time of concerns that immune escape mutants, such as the Omicron strain, may emerge from chronically infected patients with weakened immune systems.

“Thus, the immunosuppressed and their close contacts should be target groups for therapeutic and preventive interventions, including community-level outreach and educational efforts,” said Dr Dimitrios Farmakiotis, an infectious disease clinician at the Warren Alpert Medical School of Brown University and a senior author of the study.

Study details

COVID-19 Vaccination and Breakthrough Infections in Patients with Cancer

A.L. Schmidt, C. Labaki, CY Hsu, Z. Bakouny, N. Balanchivadze, S.A. Berg, S. Blau, A. Daher, T. El Zarif, C.R. Friese, E.A. Griffiths, J.E. Hawley, B. Hayes-Lattin, V. Karivedu, T. Latif, B.H. Mavromatis, R.R. McKay, G. Nagaraj, R.H. Nguyen, O.A. Panagiotou, A.J. Portuguese, M. Puc, M. Santos Dutra, B.A. Schroeder, A. Thakkar, E.M. Wulff-Burchfield, S. Mishra, D. Farmakiotis, Yu Shyr, J.L. Warner, T.K. Choueiri.

Published in Annals of Oncology on 24 December 2021


Patients with cancer who develop breakthrough COVID-19 after full vaccination remain susceptible to severe outcomes.

Haematologic malignancies are over-represented among vaccinated patients with cancer who develop breakthrough COVID-19.

Vaccination of close contacts, masking, boosters, and social distancing are needed to protect patients with cancer.


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 with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harbouring haematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19.

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.


Annals of Oncology article – COVID-19 Vaccination and Breakthrough Infections in Patients with Cancer (Open access)


See more from MedicalBrief archives:


CDC panel backs third Pfizer and Moderna shot for the immunocompromised


Monoclonal antibodies effective for breakthrough COVID cases — Mayo Clinic


COVID-19 vaccines highly effective in most people in clinical risk groups — Massive UK study


FDA green-lights third jab for immunocompromised people



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