COVALENCE STUDY: Immunogenicity and Reactogenicity of a COVID-19 mRNA Vaccine in an Open-Label Cohort of Long-Survivor Patients with Metastatic Lung Cancer

<b>Background:</b> As COVID-19 has become an epidemic, we conducted an open-label study aimed to identify immunogenicity and reactogenicity of boosters of the BNT162b2 vaccine in a real-world cohort of long-survivor metastatic lung cancer patients (LS-mLC pts). <b>Methods and Analysis:</b> According to the timing of the booster dose (BD) and SARS-CoV-2 infection (Cov-I) during anticancer treatment (ACT), between October 2021 and February 2022, we prospectively enrolled 166 cancer patients into five parallel cohorts. The primary endpoints were seroprevalence of IgG Anti-spike-RBD (anti-S IgG) at two pre-defined timepoints (T1: +30-90 days after BD; T2: +6 months +/- 4 weeks after BD). As an exploratory endpoint, we compared the median pre-vaccination value of four cytokines (IL-6, IL-2R, TNF-α, IL-10) with post-BD values in immunotherapy-treated pts (IO-pts). <b>Results:</b> The anti-S IgG seropositivity rate was 100% at T1 and 98.8% at T2. After 6 months, hybrid immunisation was associated with a higher median anti-S IgG titre compared to vaccine-alone-induced seroconversion (<i>p</i> < 0.0001). In uninfected pts, the median anti-S IgG titre was significantly lower in IO-pts compared to non-IO-pts (<i>p</i> = 0.02); no difference was found when comparing myelosuppressive or not ACT. Among the 68 IO-pts, 5 pts (7.3%) showed a significant increase (≥1.5 fold) of at least two cytokines in post-BD samples, without reporting ir-AEs. <b>Conclusions:</b> Boosters of the COVID-19 mRNA vaccine were effective and safe. In IO-pts without recent Cov-I, additional BDs should be considered to prolong serological immunity.