CORSA study finds spike-specific blunted immune responses in lymphoma patients after SARS-CoV-2 vaccine.

Introduction: Hematological patients are at higher risk of severe SARS-CoV-2 infection and exhibit impaired vaccine responses due to disease and therapy. Treatments like Rituximab are known to compromise immune function, reducing the generation of protective antibodies. Methods: In the CORSA trial, we evaluated humoral and cellular responses to messenger RNA vaccines against SARS-CoV-2 in 77 patients with hematological malignancies receiving active treatment and in matched healthy controls. Peripheral blood samples were processed to assess Spike-specific immunoglobulin G titers, T-cell responses by enzyme-linked immunospot assay, and T-cell receptor repertoire sequencing from baseline to six months after vaccination to determine clonal breadth and depth of Spike-specific T-cell receptor clones. Results: Seroconversion occurred in only 8% and 21% of patients after the first and second dose, compared to 93% and 100% of healthy controls. Despite poor antibody responses, 69% of seronegative patients showed measurable T-cell activity, suggesting some level of vaccine-induced protection. Spike-specific TCR repertoire analysis in lymphoma patients (LP) and HC revealed significantly broader clonal breadth (p = 0.0013) and higher clonal depth (p = 0.0265) in HC at day 50 versus baseline, while blunted diversification in LP (p = 0.0407). Conclusions: Lymphoma patients showed significantly weaker Spike-specific clonal responses and reduced diversity compared with healthy controls, supporting the association with increased patient vulnerability.