Subset of patients with lung cancer have poor response to COVID-19 vaccines

Most patients with non-small cell lung cancer had an adequate antibody response to COVID-19 vaccines, research published in Journal of Clinical Oncology showed.

However, up to a quarter of patients had a poor response to vaccines, including low neutralizing antibodies to the B.1.1.529 omicron variant. Poor responders showed increased neutralizing antibodies to omicron variants that declined precipitously 3 months after booster doses, highlighting a high-risk population in need of optimized vaccination strategies, the researchers noted.

Background

Patients with lung cancer are “among those at greatest risk” for adverse outcomes if they contract COVID-19 because of typically reduced lung function, according to Rafi Ahmed, PhD, professor in the department of microbiology and immunology at Emory University School of Medicine, director of Emory Vaccine Center and co-leader of Cancer Immunology Research Program at Winship Cancer Institute of Emory University.

Given this elevated risk, Ahmed told Healio that his group wanted to know how patients with lung cancer would respond to commercially available mRNA vaccines and booster doses.

Methodology

Ahmed and colleagues administered SARS-CoV-2 mRNA vaccines to 82 patients with NSCLC and 53 healthy volunteers.

The investigators collected longitudinal peripheral blood samples subsequently evaluated for binding and neutralizing antibody responses using commercially available assays.

Key findings

Although most patients with NSCLC showed binding and neutralizing antibody titers comparable with those of the healthy controls after a series of two initial mRNA vaccines, 25% had poor responses to vaccination that resulted in six- to sevenfold lower titers (P .0001).

The investigators noted no significant differences in antibody response depending on previous cancer treatment.

Patients showed significantly lower neutralizing antibody titers to COVID-19 variants — including B.1.617.2 (delta), B.1.351 (beta), and B.1.1.529 (omicron) (P .0001) — compared with the 614D (wild-type) strain.

Patients who received vaccine boosters showed a significant increase (P .0001) in binding and neutralizing antibody titers to the COVID-19 wild-type strain and omicron variant. This increase in neutralizing antibodies decreased five- to sevenfold within 2 to 4 months of receiving a booster dose, the researchers noted.

Clinical implications

The key takeaway from the study is surprising, Ahmed said. Given the deleterious effects various forms of anticancer treatment have on the body's immune system, he was encouraged by the fact that approximately 75% of patients with lung cancer responded to COVID-19 vaccination.

“But nearly a quarter of those we studied had poor responses, with many patients having very poor responses to vaccines,” he told Healio. “[We] don't know why there is such variability among patients with lung cancer but hope to explain these reasons as part of longer follow-up studies.”

For example, Ahmed said his group is currently looking at T cell responses to the COVID-19 vaccines in patients with lung cancer to determine whether those who did not produce adequate antibody responses also show a defect in T-cell responses after vaccination.

"Even after boosters, patients with lung cancer who are poor responders to COVID-19 vaccines still never quite catch up to producing antibody levels similar to those who respond well or healthy controls,” he noted.

“The booster helped for some patients who were initial poor responders and is definitely an important part of clinical care for patients with lung cancer,” he added. “However, I would like to see future iterations of the vaccine be omicron-specific to help produce more useful antibodies.”

For more information:

Rafi Ahmed, PhD, can be reached at rahmed@emory.edu.