Immunogenicity after the third dose of mRNA-based COVID-19 vaccines in patients with solid tumors

ABSTRACT

Background: Despite of the administration of multiple doses of vaccines (vax), cancer patients (pts) are a group at high risk of COVID-19 complications. The aim of this study is to evaluate the factors associated with the humoral response to the 3rd dose (D) of mRNA-based vax in cancer pts during or after active treatment. Patients and Methods: Single institution, prospective study conducted at the L. Sacco Hospital, Milan, between 5/2021-4/2022. 30 days after the 2nd and 30 days after the 3rdD of BNT162b2 or mRNA-1273 (selected based on local pharmacy availability), seric levels of 3 antibodies (Ab) were measured in solid tumors pts during or after the active treatment, by a fluorescence bead-based assay. Anti-S and anti-RBD IgG to determine the humoral response to vax, anti-N IgG to identify a previous exposure to SARS-Cov-2. Primary objective: to assess the seroconversion (SC) rate and the Ab titres after 3rdD. Secondary Objectives: to detect any relation between the 3rdD response and pre-defined pts variables;to evaluate the humoral response to 3rdD in pts not responding to the 2ndD. Result(s) 99 of 110 pts were evaluated 67.7% female, median age 63 ys, 49.5% breast cancer, 67.7% advanced stage. Active treatment 40.4% biologic agent, 23% chemotherapy (alone or combination), 11.1% hormone. 3rdD vax type 74.8% BNT162b2, 25.2% mRNA-1273. SC after 3rdD was obtained in 99% of pts. The use of GCSF was associated with a lower amount of anti-RBD IgG (p=0.03). A 6 vs 5 months interval between 2nd and 3rdD was correlated with higher anti-S IgG level (p<0.001). The heterologous vax regimen was associated with higher rate of anti-S IgG (p=0.04), especially the sequence mRNA- 1273 x 2 -> BNT162b2 (p=0.001). No significant correlation at the multivariate analyses was found between Ab levels and the other variables tested (age, BMI, cancer type, tumor stage, use of steroids, previous exposure to SARS-CoV-2, anti-cancer therapy, neutropenic potential of the therapy). 21/22 pts not responding to the 2ndD obtained SC after 3rdD. Conclusion(s) 3rdD of anti-COVID-19 vax is effective in cancer pts with solid tumors undergoing or after recent treatment. In this group the 3rdD oversteps all the negative influence of the factors related to the 2ndD vax failure, achieving the same response of the healthy population and demonstrating efficacy in not previously responders, too. The better performance of the heterologous vax regimen could be due to an exposition to a wider range of epitopes.