Fourth COVID-19 vaccination protects patients with cancer
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A fourth dose of the COVID-19 vaccine increased humoral immunity among patients with solid and hematologic cancers, according to study results published in JAMA Oncology.
However, passive immunization with the long-acting monoclonal antibodies tixagevimab and cilgavimab (Evusheld; AstraZeneca) did not appear effective against omicron sublineages BA.1 and BA.4, researchers noted.
Background and methods
“We and other groups showed earlier this year that a third vaccination dose increased humoral immunity against COVID-19 in patients with cancer,” Matthias Preusser, MD, professor of medical oncology and head of the clinical division of oncology at Medical University of Vienna, told Healio. “However, new virus variants of concern keep emerging and are a particular threat to immunocompromised patients, such as those with cancer. We therefore sought to investigate whether a fourth vaccine dose, or antibody-based preexposure prophylaxis, was capable of increasing the immunity in this patient population.”
Preusser and colleagues compared antibody levels against the receptor-binding domain of the spike protein of COVID-19 hu-1 and omicron sublineages BA.1 or BA.4 among 72 patients (median age, 74 years; 65.3% men) with cancer who received a fourth dose of COVID-19 vaccination (n = 54) or tixagevimab and cilgavimab (n = 18). Most of those who received the fourth vaccination (n = 33) had hematologic malignant neoplasms, whereas 21 had solid tumors.
Investigators also assessed the inhibition of the interaction between receptor-binding domains and the receptor angiotensin-converting enzyme 2.
Findings
Results showed median anti-receptor-binding domains increased from before to after fourth vaccination against omicron sublineages BA.1 (0.154 optical density to 0.969 optical density; P = .02) and BA.4 (0.245 to 0.966; P = .02) among patients with hematologic malignant neoplasms undergoing B cell–targeted therapy. Of note, researchers observed no other differences in antibody levels among those with other hematologic diseases.
Among those with solid malignant neoplasms, researchers identified pronounced increases in median anti-receptor-binding domains before vs. after the fourth vaccination dose against variants hu-1 (1.157 optical density vs. 1.438 optical density; P = .02), BA.1 (0.721 vs. 1.026; P = .003) and BA.4 (0.556 vs. 1.22; P = .002).
Moreover, the potential inhibition of the interaction between receptor-binding domains and the receptor angiotensin-converting enzyme 2 appeared higher after the fourth vaccination dose among patients with hematologic disease and solid tumor cancers, especially for sublineages BA.1 and BA.4, according to the researchers.
Researchers further observed median inhibition of receptor-binding domains and the receptor angiotensin-converting enzyme 2 with tixagevimab and cilgavimab of 99.9% for sublineage hu-1, 34.9% for BA.1 and 15.4% for BA.4.
“We recommend a fourth COVID-19 vaccine dose to our patients with solid and hematologic cancers, based on our findings,” Preusser said. “However, we discourage passive immunization with tixagevimab and cilgavimab, because we saw very limited blocking activity against currently circulating COVID-19 variants.”
Future research
Next steps include the examination of the cellular immune response to the fourth vaccination dose to obtain a better understanding of the potential memory effects on the immune system, Preusser said.
“In addition, we are planning studies on long-COVID-19 and humoral immune responses to adapted vaccines and a fifth vaccination dose, which is also already being considered in immunocompromised individuals,” he added.
For more information
Matthias Preusser, MD, can be reached at matthias.preusser@meduniwien.ac.at.
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