Immunogenicity and clinical efficacy of anti-SARS-CoV-2 vaccination in patients with hematological malignancies: results of a prospective cohort study of 365 patients

This prospective cohort study evaluated the humoral and cell-mediated immune response and clinical efficacy of anti-SARS-CoV-2 vaccination in adult patients with hematological malignancies (HMs). A total of 365 patients who received a double-dose mRNA vaccine were analyzed. Seroconversion was achieved in 82% of patients, with lower rates observed in those receiving anti-CD20 therapies (4%), BTK inhibitors (42%), JAK2 inhibitors (68%), and daratumumab-based therapies (69%). Booster vaccination led to seroconversion in 37% of initially seronegative patients. Cellular immunity assessment via ELISpot and flow cytometry indicated the presence of spike-specific memory T-cells, albeit at lower levels in seronegative patients. During a median follow-up of 269 days, 8% of patients developed SARS-CoV-2 breakthrough infections, with a significantly increased incidence after the emergence of the Omicron variant. Seropositivity after vaccination correlated with a lower risk of breakthrough infection, while cellular immunity did not show a clear protective effect. Comparing vaccinated and pre-vaccination cohorts, vaccinated patients exhibited significantly lower rates of severe disease (10% vs. 33%), hospitalization (17% vs. 50%), and shorter disease duration (16 vs. 22 days). The findings confirm reduced vaccine immunogenicity in HM patients, particularly those undergoing active treatment, but highlight its protective effect against severe Covid-19 outcomes.