Identifying Cancer Patients Most at Risk for Breakthrough COVID

Megan Brooks

December 23, 2022

Editor's note: Find the latest COVID-19 news and guidance in Medscape's Coronavirus Resource Center.

Patients with cancer who had undetectable antibody responses after COVID-19 vaccination face a threefold higher risk for SARS-CoV-2 breakthrough infection and a more than sixfold higher risk for infection-related hospitalization than those with a positive antibody response, a new study reveals.

The findings support the use of SARS-CoV-2 spike protein antibody testing for identifying patients with the lowest level of antibody-derived protection and immunity from the virus, the researchers conclude.

"Antibody testing could empower these individuals to take additional preventive measures to reduce their risk of infection," write lead author Lennard Y. W. Lee, DPhil, with the University of Oxford, United Kingdom, and colleagues.

The study was published online December 22 in JAMA Oncology.

People who are immunocompromised, including patients with cancer, are much more likely to experience breakthrough infection following COVID-19 vaccination. However, identifying people with the lowest degree of protection and who are thus most at risk for breakthrough infection remains less clear.

In the current study, Lee and colleagues aimed to understand whether the risk of breakthrough SARS-CoV-2 infection or hospitalization among patients with cancer was linked to their antibody responses following vaccination.

Using the UK National COVID Cancer Antibody Survey, the researchers evaluated 4249 SARS-CoV-2 spike protein antibody test results from 3555 patients with cancer and 294,230 test results from 225,272 noncancer control patients in the general population. The antibody tests were performed after the second or third vaccine dose.

In both the cancer and the control groups, individuals who had received a third dose had significantly higher antibody titers than those who had received only two doses (11,146.5 vs 8765 U/mL for the cancer cohort and 23,667 vs 12,126.0 U/mL for the control cohort).

Lee and colleagues found that patients with cancer were significantly more likely to have undetectable antispike antibody responses than control patients who did not have cancer (4.68% vs 0.13%; P < .001).

Patients with leukemia or lymphoma had the lowest antibody titers — 19.3% had no detectable vaccine antibody response, compared with 4.2% of patients with solid organ tumors and 0.1% of control patients. Patients who were receiving systemic anticancer therapy and those with stage IV cancers were also more likely to have lower antibody titers.

Following multivariable adjustments, patients with cancer who had an undetectable antibody response had a threefold greater risk for SARS-CoV-2 breakthrough infection (odds ratio [OR], 3.05; P < .001) and a 6.5 times greater risk of SARS-CoV-2–related hospitalization (OR, 6.48; P < .001) than those with positive antibody responses.

Overall, in the cancer cohort, 259 patients had a breakthrough infection, and 55 patients had a SARS-CoV-2–related hospitalization following their antibody test. Those who were hospitalized had significantly lower median antibody titers than those who were not (147.0 U/mL vs 10,961.0 U/mL).

The findings suggest that SARS-CoV-2 spike protein antibody testing "can identify patients with cancer who have the lowest level of antibody-derived protection and immunity from SARS-CoV-2 and COVID-19," the authors conclude. They note that, to their knowledge, this is the first study to demonstrate such an association.

The authors acknowledge that they did not thoroughly assess the time between vaccination and antibody tests or control for the effect of viral variants. The study took place at the end of the Delta wave and the beginning of the Omicron wave.

Nonetheless, Lee and colleagues conclude that "wider access to antibody testing for individuals with cancer should be evaluated." This "could help inform national guidance for clinicians advising patients and may provide a risk surveillance strategy that can be used to guide vaccination booster programs."

The findings may also help individuals make more informed choices about personal risk and precautions to reduce their risk of infection and transmission.

The authors note, however, that antibody testing is only "one part of a larger strategy that includes collective efforts such as ventilation, filtration and 2-way masking, which will make life safer for vulnerable and immunocompromised patients."

The authors of an accompanying editorial propose additional strategies to support the needs of the most vulnerable, including efforts to expand vaccine counseling and access, improve access to antibody testing, and provide education on a range of topics, from how the virus spreads to how to reduce in-home transmission.

Overall, the editorialists conclude that the study provides "compelling" evidence that cancer patients are more vulnerable to COVID-19 and suggest that "vaccines and antibody testing are key components of a comprehensive strategy to protect the most vulnerable oncology patients during the ongoing COVID-19 pandemic."

The study was supported by the University of Oxford, the University of Birmingham, the University of Southampton, the UK Health Security Agency, and Blood Cancer UK. A complete list of authors' disclosures is available with the original article. The editorial writers have disclosed no relevant financial relationships.

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