143 Long-term cellular and humoral responses to SARS-CoV-2 vaccinations in patients with solid malignancies undergoing chemotherapy

<h3>Background</h3> While SARS-CoV-2 vaccines are highly effective in healthy individuals, the magnitude and durability of humoral and cellular responses in patients with solid malignancies receiving chemotherapy remain less known. Emerging data suggest that cancer patients may not mount adequate immune response after SARS-CoV-2 vaccination. Additionally, most studies focused on humoral responses, while data regarding T cell and longitudinal immune responses remain scarce. In this study, we evaluated humoral and cellular responses in patients with solid tumors receiving chemotherapy compared to healthy individuals up to one year after vaccinations. <h3>Methods</h3> Patients aged ≥18 who were willing to receive the SARS-CoV-2 vaccine were enrolled. The cancer cohort included patients with confirmed solid tumors receiving chemotherapy. Patients had blood draws before, 1, 6, and 12 months after vaccinations. Anti-SARS-CoV-2 immunoassays were used to detect antibodies. Human IFN-γ assay was used to determine antigen-specific T cell responses. Data were compared between groups using the Mann-Whitney test for continuous variables and Fisher’s exact test for categorical variables. <h3>Results</h3> 67 subjects (47 cancer patients and 20 healthy individuals) were included. One month post-vaccination, 93% of cancer patients and 100% of healthy individuals demonstrated a positive humoral response. While the positivity rate was not significantly different, cancer patients had significantly lower spike antibodies than healthy individuals (median 391 µg/mL vs. 2500 µg/mL, P = 0.003). However, this difference diminished at 6 months when cancer patients had increased antibodies compared to decreased antibodies in the healthy cohort (median 1140.5 µg/mL vs. 788.0 µg/mL, P = 0.98) and at 12 months. Cancer patients developed a similar antigen-specific T cell response as healthy individuals at 1 month (median spike T cells 224.6/1x10⁶ vs. 379.5/1x10⁶, P = 0.17), 6 months (360/1x10⁶ vs. 137.5/1x10⁶, P = 0.21) and 12 months. There were no significant differences when comparing patients aged ≤ 55 years vs. &gt;55 years, stages I-III vs. IV, single vs. multiple chemotherapy, and Pfizer vs. Moderna vaccines. There was a significant moderate correlation (Spearman correlation 0.45, P = 0.002) between neutralization and antibody levels at 12 months. However, despite cancer patients having a significantly higher COVID risk score, there were no significant differences in COVID-19 infections and hospitalization rates between cancer patients and healthy individuals. <h3>Conclusions</h3> Despite initial impaired antibody responses to SARS-CoV-2 vaccinations, patients with solid malignancies receiving chemotherapy effectively generated long-term cellular and humoral responses by 6 and 12 months, leading to similar infection and hospitalization rates compared to healthy individuals. <h3>Ethics Approval</h3> This study (ID: 20-012037) was approved by the Mayo Clinic Institutional Review Board and was conducted in compliance with the Good Clinical Practice, Declaration of Helsinki, and the International Conference on Harmonization. Written informed consent was voluntarily obtained from all participants.