The impact of cyclin-dependent kinases 4 and 6 inhibitors in the immune response to mRNA SARS-CoV-2 vaccine in women with breast cancer.

Abstract

Abstract Introduction: Patients with cancer have a higher risk of complications and death from coronavirus disease 2019 (COVID19), thus vaccination is crucial in this population. Oncologic therapies can affect vaccination response, but few data are available about the immune response to mRNA SARS-CoV-2 vaccines in patients with breast cancer receiving cyclin-dependent kinases 4/6 inhibitors (CDK4/6i). Our study aimed to assess the immunogenicity and safety of the mRNA-1273 vaccine in patients treated with CDK4/6i in comparison with a group of volunteer health workers. Methods: We conducted a prospective, single-center study including patients with breast cancer treated with CDK4/6i and a comparative group of health care workers (HCW). Blood samples were collected before and after first dose administration, and after second dose. The primary endpoint was to compare the rate and magnitude of humoral and T-cell responses after full vaccination. Neutralizing antibodies titers, the correlation between neutralizing and anti-S antibodies, the incidence of COVID-19 after vaccination, and safety were defined as secondary objectives. Results: No differences were observed in the rate of either anti-S or neutralizing antibodies after full vaccination, being 100% in both groups. A positive correlation was found between neutralizing and anti-S antibodies. However, the rate of anti-S CD4 and CD8 T-cell response after complete vaccination was a 15% lower in the CDK4/6i group, although differences were not statistically significant (CD4 T-cell response 69.2% vs 84.6%; p 0.324; anti-S T-cell CD8 response 69.2% vs 84.6%; p 0.324). No differences in the incidence of COVID-19 after vaccination were found (19.2% vs 11.5%, p 0.703). Patients with vaccine breakthrough showed lower levels of anti-S antibody after the first dose (492.29 vs 157.96; p 0.029) and lower titers of neutralizing antibodies after full vaccination (p 0.068). The rate of adverse events was higher in patients treated with CDK4/6i. No serious adverse events were reported in any of the two groups. Conclusion: While a robust humoral response was observed in the CDK4/6i group, a limited T cell response was found, without differences in the rate of subsequent COVID-19. Further insight into the underlying mechanisms is crucial to improve breast cancer patients’ protection and to adjust vaccination strategies in this specific population.