Third Dose of COVID-19 Vaccine Increases Neutralizing Antibodies Against Omicron in Cancer Patients

A third dose of the Pfizer-BioNTech COVID-19 vaccine increases the level of neutralizing antibodies against the omicron variant in patients with solid tumors or hematologic malignancies, according to research published in The Lancet.¹

Previous data demonstrated that a third dose of the Pfizer-BioNTech vaccine (BNT162b2) increased neutralizing antibodies against SARS-CoV-2 variants such as B.1.1.7 (alpha), B.1.351 (beta), and B.1.617.2 (delta) in patients with cancer.²

For the current analysis, researchers evaluated the effect of a third dose on levels of neutralizing antibodies against the B.1.1.529 (omicron) variant. They also compared these results to results with the delta variant and wild-type SARS-CoV-2.

The study included 199 patients from the CAPTURE study, 115 of them with solid tumors and 84 with hematologic malignancies. All patients received a third dose of the Pfizer-BioNTech vaccine. They had received a primary 2-dose series with either the Pfizer-BioNTech or Oxford-AstraZeneca (ChAdOx1) vaccines.

The third vaccine dose was given a median of 176 days after the second dose. There were 23 patients who had a previous SARS-CoV-2 infection, all of which occurred prior to their second vaccine dose with a variant other than omicron.

Neutralizing antibody titers were measured before (median, 11 days) and after administration of the third dose (median, 23 days). Live-virus micro-neutralization assays were used to evaluate neutralizing antibody response to viral variants.

Results

Among patients with solid tumors, the proportion who had neutralizing antibodies against the omicron variant rose from 37% after 2 vaccine doses to 90% after 3 doses. For patients with hematologic cancers, the percentage rose from 19% after 2 doses to 56% after 3 doses.

In comparison, the percentage of patients with solid tumors who had neutralizing antibodies against the delta variant rose from 56% after 2 doses to 97% after 3 doses. For patients with hematologic cancers, the percentage rose from 39% to 71%.

The percentage of patients with solid tumors who had neutralizing antibodies against wild-type SARS-CoV-2 rose from 97% after 2 doses to 99% after 3 doses. For patients with hematologic cancers, the percentage decreased from 89% to 86%.

Of the patients with hematologic malignancies, 81% had no detectable neutralizing antibodies against omicron after 2 vaccine doses. Of these patients, 45% developed neutralizing antibodies after their third dose.

Undetectable neutralizing antibodies against omicron in patients with hematologic cancers after their third vaccine dose was associated with receiving anti-CD20 monoclonal antibody treatment within 12 months, receiving BTK inhibitor treatment within 28 days, and progressive disease after recent anticancer therapy. There was no association with the type of hematologic malignancy, the manufacturer of the primary COVID-19 vaccine series, or patient age.

There were 4 cases of breakthrough delta infection after 2 vaccine doses, which were deemed mild or asymptomatic. All patients developed detectable neutralizing antibodies against omicron after infection, “suggesting that two vaccine doses and a third antigenic challenge via delta infection can lead to a functional immune response against omicron,” the researchers wrote.

They concluded that “a third vaccine dose boosted the neutralizing response against omicron in patients with cancer, but the effect was blunted in patients with blood cancer compared to those with solid cancer.”

Given this, and the high transmissibility of the omicron variant, the researchers suggested that mitigation measures other than vaccination remain important to protect patients with hematologic cancers.

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

References

1. Fendler A, Shepherd STC, Au L, et al. Omicron neutralizing antibodies after third COVID-19 vaccine dose in patients with cancer. Lancet. Published online January 25, 2022. doi:10.1016/S0140-6736(22)00147-7
2. Fendler A, Shepherd STC, Au L, et al. Adaptive immunity and neutralizing antibodies against SARS-CoV-2 variants of concern following vaccination in patients with cancer: The CAPTURE study. Nat Cancer. 2021;2:1321-1337. doi:10.1038/s43018-021-00274-w

This article originally appeared on Cancer Therapy Advisor