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

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.

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.

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).

Lymphoma patients showed significantly weaker Spike-specific clonal responses and reduced diversity compared with healthy controls, supporting the association with increased patient vulnerability.