Humoral and T-cell immune responses to coronavirus disease 2019 vaccines in patients with hematological malignancies

Recent studies have demonstrated that patients with hematological malignancies (HM) exhibit significantly impaired humoral immune responses after coronavirus disease 2019 (COVID-19) vaccination. Although booster doses and cellular immune responses have been increasingly studied, few analyses have concurrently evaluated both humoral and cellular immunity in patients receiving bendamustine, bispecific antibodies, or CAR-T therapies. We aimed to assess the humoral immunogenicity, T-cell immune response, and booster effect after COVID-19 vaccination in patients with B-cell lymphoma undergoing immunochemotherapy or novel agent treatment.

Serum antibodies to the severe acute respiratory syndrome coronavirus 2 spike protein (S-IgG) were measured after the second and booster (third) mRNA vaccinations, and specific T-cell responses were measured using the enzyme-linked immunosorbent spot method.

Forty-six of 114 patients (40%) acquired antibodies. Age < 65 years (odds ratio 8.99) and CD19 ≥ 50/μL (odds ratio 19.7) were independent predictors of response. To support the selection of this threshold, operating characteristic curve analysis was performed and confirmed CD19 ≥ 50/μL as a clinically meaningful discriminator despite a lower statistical cutoff. Even in some patients who did not develop antibodies, T-cell responses were observed (36% after two doses; 45.5% after the booster). The booster vaccine enhanced antibody (40% to 62.9%) and T-cell (47.2% to 57.6%) responses.

This study provides confirmatory real-world evidence that CD19 recovery is a key determinant of humoral response, while vaccine-induced T-cell immunity may be preserved even in antibody-nonresponders, supporting continued vaccination efforts in this high-risk population.