Long-term immune response to mRNA anti-SARS-CoV-2 vaccination in patients with cancer

Introduction: Patients with cancer are at increased risk of morbidity and mortality from COVID-19 but were underrepresented in pivotal vaccine trials. Data on the magnitude and determinants of immune responses to mRNA SARS-CoV-2 vaccination in this population remain limited. Methods: I-SPARC is a prospective, phase IV clinical trial evaluating humoral and cellular immune responses to mRNA SARS-CoV-2 vaccination in 115 patients with cancer, including those receiving systemic therapy and those in remission. Anti-Spike antibody titers were measured longitudinally, and immunophenotyping was performed to assess T and B cell subsets. Clinical outcomes, including SARS-CoV-2 infection, were recorded. Results: All patients developed detectable anti-Spike antibodies, although absolute titers varied by cancer type and treatment. Patients with hematologic malignancies and/or receiving chemotherapy had the lowest anti-Spike antibody levels. Booster doses significantly increased titers, particularly in patients in remission or receiving non-cytotoxic therapies. Prior SARS-CoV-2 infection and the number of vaccine doses were associated with better responses. Immunophenotyping confirmed vaccine-induced expansion of memory T and B lymphocyte subpopulations. SARS-CoV-2 infection occurred in 16% of our cohort, with infrequent severe cases. Discussion: mRNA SARS-CoV-2 vaccines elicit robust humoral and cellular immune responses in patients with cancer, despite variability according to disease type and treatment. These findings support the use of booster strategies and provide a rationale for tailored vaccination approaches in immunocompromised populations.