Influenza Vaccination Strategy for Patients With Hematologic Malignancy

Comparison of Immunogenicity of Different Influenza Vaccines in Patients With Hematologic Malignancies

This randomized controlled trial evaluates and compares the immunogenicity of three different influenza vaccine formulations: high-dose trivalent (HD-IIV3), MF59-adjuvanted quadrivalent (aIIV4), and standard-dose trivalent (SD-IIV3) vaccines. The study population consists of patients with hematologic malignancies, including those undergoing autologous stem cell transplantation or CAR-T cell therapy. The primary goal is to identify which vaccine strategy elicits the most robust antibody and T cell-mediated immune responses in this severely immunocompromised population

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