Patients with cancer have a higher risk of breakthrough COVID-19 after vaccination when compared with patients who don’t have cancer, according to research published in the Journal of Clinical Oncology.

The risk of breakthrough COVID-19 was higher for patients with hematologic malignancies than for those with solid tumors. 

The risk was also higher among partially vaccinated patients, those who received the Pfizer-BioNTech vaccine, and those who had been treated with proteasome inhibitors, immunomodulators, monoclonal antibodies, and bone marrow transplant.

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To conduct this study, researchers used a nationally representative cohort of patients made available through the National COVID Cohort Collaborative (N3C).

The N3C cohort included 6860 cases of breakthrough COVID-19 among 2787 fully vaccinated patients and 4073 partially vaccinated patients. The cohort included 1460 patients with cancer, 867 who were fully vaccinated and 593 who were partially vaccinated.

The cancer cohort had a significantly greater proportion of fully vaccinated patients with breakthrough COVID-19 compared with the non-cancer cohort — 59.4% and 35.6%, respectively (odds ratio [OR], 2.65; P <.0001).

In an adjusted analysis, the risk of breakthrough COVID-19 was significantly higher among patients with hematologic malignancies (OR, 4.64; P <.0001) or solid tumors (OR, 1.12; P =.0231) than among patients without cancer.  

The risk of severe COVID-19 outcomes was also higher among patients with hematologic malignancies (OR, 1.45; P =.0124) or solid tumors (OR, 1.33; P =.0046).

Patients with hematologic malignancies had an increased risk of breakthrough COVID-19 compared with solid tumor patients (ORs ranged from 2.07 for lymphoma to 7.25 for lymphoid leukemia; P ≤.0001 for all). 

After the second vaccine dose, the breakthrough risk decreased for all cancers (OR, 0.04; P <.0001). The Moderna COVID-19 vaccine was more effective for preventing breakthrough COVID-19 than the Pfizer-BioNTech vaccine (OR, 0.66; P <.0001), particularly for patients with multiple myeloma (OR, 0.35; P =.0082).

The risk of breakthrough COVID-19 was higher among patients who received proteasome inhibitors (OR, 10.28; P <.0001), immunomodulators (OR, 6.19; P <.0001), monoclonal antibodies (OR, 2.33; P <.0001), or bone marrow transplant (OR, 5.30 within 6 months, 3.81 from 6 months to 1 year, and 6.81 over 1 year; P <.0001 for all).

“Real-world evidence shows that patients with cancer, especially hematologic malignancies, are at higher risk for developing breakthrough infections and severe outcomes,” the researchers concluded. “Further work is needed to assess boosters and new SARS-CoV-2 variants.”

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Song Q, Bates B, Shao YR, et al. Risk and outcome of breakthrough COVID-19 infections in vaccinated patients with cancer: Real-world evidence from the National COVID Cohort Collaborative. Published online March 14, 2022. doi:10.1200/JCO.21.02419