Influenza Vaccination Strategy for Patients With Hematologic Malignancy

Patients with hematologic malignancies face a 3-10 times higher risk of influenza infection and a 5-20 times greater rate of severe complications compared to the general population, owing to disease- and treatment-related immunosuppression. Although high-dose and adjuvanted influenza vaccines have been proposed to overcome suboptimal vaccine responses in this population, robust comparative evidence remains lacking - particularly following recent clinical trials which did not demonstrate superiority of adjuvanted vaccine over standard-dose vaccine in terms of antibody response. Critically, T cell-mediated immune responses, which may serve as an independent correlate of protection especially in B cell-depleted patients (e.g., post-CAR-T therapy), have not been comprehensively evaluated in prior trials.

This randomized controlled trial aims to compare the immunogenicity of three influenza vaccine formulations - high-dose trivalent inactivated vaccine (HD-IIV3; Efluelda), MF59-adjuvanted quadrivalent inactivated vaccine (aIIV4; Fluad Quadrivalent), and standard-dose trivalent inactivated vaccine (SD-IIV3) - in patients with hematologic malignancies including lymphoma, leukemia, plasma cell disorders, and those undergoing autologous stem cell transplantation or CAR-T cell therapy. Immunogenicity will be assessed by both antibody responses (HAI-based GMT, seroconversion, seroprotection) and cellular immune responses (polyfunctional CD4+ and cytotoxic CD8+ T cells via IFN-γ/TNF-α/IL-2 intracellular cytokine staining of PBMCs) at baseline, Day 28, Day 180, and Day 365.

Inclusion criteria

• Adults aged 19 years or older
• Confirmed diagnosis of hematologic malignancy, including:

non-Hodgkin lymphoma, Hodgkin lymphoma, acute leukemia, chronic leukemia, or plasma cell disorders

Exclusion criteria

• Difficulty with repeated venipuncture or blood sampling (e.g., poor vascular access or bleeding tendency)
• Cognitive or psychiatric impairment precluding understanding of or cooperation with study procedures
• Known hypersensitivity to influenza vaccine components
• Influenza vaccination within the preceding 6 months
• Any other condition deemed clinically inappropriate for study participation at investigator discretion