Influenza-Specific T-Cell Responses to Vaccination Are Independent of Underlying Hematological Malignancy: Analysis of a Randomized Influenza Vaccination Trial

Abstract Background There are few in-depth immunogenicity analyses of novel influenza vaccination strategies in high-risk patients with hematological malignancy (HM). Methods Participants receiving treatment for active HM (multiple myeloma [MM], chronic lymphocytic leukemia [CLL], or non-Hodgkin lymphoma [NHL]) in a randomized controlled trial of 2 doses of adjuvanted quadrivalent inactivated influenza vaccine (QIV) versus 2 doses of standard-dose QIV during 2022 were included. Hemagglutination (HA) inhibition assay and HA probe–specific B-cells were compared at baseline and 1, 2, and 6 months after the first vaccine dose (visits 1–4). A subset underwent ex vivo live virus infection of peripheral blood mononuclear cells at visits 1 and 3 with A/H1N1 and A/H3N2 to assess interferon (IFN) γ–producing CD4+ T cells, CD8+ T cells, natural killer cells, CD161+TRAV1-2+ mucosal-associated invariant T (MAIT)–like T cells and γδ T cells. Results In total, 62 patients with HM were analyzed (32 in the adjuvanted-dose and 30 in the standard-dose group), 13 (21.0%) with CLL, 24 (38.7%) MM, and 25 (40.3%) with NHL. Participants with MM had higher geometric mean antibody titers (P < .001) and influenza-specific B-cell responses for H1, H3, and B/Victoria at visits 2 and 3 than those with CLL or NHL (P < .05). The total CD19+ B-cell and HA probe–specific B-cell counts were found to significantly predict seroconversion at visits 2 and 3. Overall, with vaccination, there was an increase in the percentage frequency of B/Victoria influenza–specific B-cells (P = .01), IFN-γ–producing CD4+ T cells (P = .01) for A/H1N1 and IFN-γ–producing MAIT-like cells (P = .003) for A/H3N2. Conclusions Influenza strain–specific cellular responses were detectable following vaccination despite expected B-cell depletion in patients receiving active treatment for HM. Clinical Trials Registration Australian New Zealand Clinical Trials Registry ACTRN12622000454774.