Effects of the third dose of SARS-CoV-2 mRNA-BNT162b2 vaccine on immune-related adverse events and disease outcomes in cancer patients receiving immune checkpoint inhibitors

Abstract Background The clinical implications of the third dose of coronavirus disease 2019 (COVID-19) vaccines in patients receiving immune checkpoint inhibitors (ICIs) are currently unknown. We performed a prospective analysis of the Vax-On-Third study to investigate the effects of antibody response on immune-related adverse events (irAEs) and disease outcomes. Methods Recipients of the booster dose of SARS-CoV-2 mRNA-BNT162b2 vaccine who had received at least one course of ICI treatment before vaccination for an advanced solid malignancy were eligible. Results The current analysis included 56 patients with metastatic disease (median age: 66 years; 71% male), most of whom had a lung cancer diagnosis and were being treated with pembrolizumab- or nivolumab-based regimens. The optimal cut-point antibody titer of 3424 AU/mL allowed a dichotomization of recipients into low-responders (Low-R, < 3424 AU/mL) or high-responders (High-R, ≥ 3424 AU/mL). After a median follow-up time of 131 days, 20% of patients experienced moderate to severe irAEs without any recrudescence of immune toxicities preceding the booster dose. The frequencies of irAE before and after the third dose did not differ, but a significant increase in the cumulative incidence of immuno-related thyroiditis was observed within High-R subgroup. On multivariate analysis, an enhanced humoral response correlated with a better outcome in terms of durable clinical benefit, which resulted in a significant reduction in the risk of disease control loss but not mortality. Conclusions Our findings would strengthen the recommendation not to change immunotherapy plans based on current or future immunization schedules, implying that all these patients should be closely monitored.