Results from a single-blind, randomised, controlled study (ACTRN12622000454774) conducted in Australia that compared two doses of adjuvanted quadrivalent inactivated influenza vaccine (QIV) with two doses of standard dose QIV in patients with multiple myeloma, chronic lymphocytic leukaemia (CLL), or non-Hodgkin’s lymphoma, who had received active therapy within the past 12 months, support the annual use of single dose QIV in patients who have not undergone haematopoietic cell transplantation (HCT).
Efforts should focus on increasing vaccination uptake according to Victoria G. Hall, MB, BS, MPH of the University of Melbourne in Parkville, VIC, Australia and colleagues, who published the findings on 15 January 2025 in The New England Journal of Medicine.
Patients with haematologic malignancies are at increased risk for severe outcomes from influenza, but have impaired immunogenicity to vaccination. In this study participants were randomly assigned in a 1:1 ratio to receive two doses of adjuvanted QIV or two doses of standard dose QIV given 21 to 28 days apart with stratification according to underlying disease during the Southern Hemisphere 2022 and 2023 influenza seasons.
A haemagglutination-inhibition assay for QIV antigens was performed at baseline and 1, 2, and 6 months after the first dose (visits 1 through 4, respectively). The primary outcome was seroconversion (defined as an increase from baseline in the antibody titre by a factor of 4) at 1 month after the second dose (visit 3).
The study team enrolled 130 participants with haematologic malignancies. The characteristics of the participants at baseline were similar in the two groups. The median age of the participants was 64 years (interquartile range, 56 to 74), and participants included 44 with multiple myeloma (33.8%), 33 with CLL (25.4%), and 53 with non-Hodgkin’s lymphoma (40.8%). Treatment history included CAR T-cell therapy in 4.6% of the participants, bispecific antibody therapy in 3.8%, and Bruton’s tyrosine kinase inhibitor therapy in 20.0%.
For the primary outcome, the percentage of participants with seroconversion at visit 3 was 37% in the adjuvanted dose group and 42% in the standard dose group for A(H1N1)pdm09 with a relative risk of 0.88 (98.75% confidence interval [CI] 0.55 to 1.55), 46% and 46% for A(H3N2) with a relative risk of 1.00 (98.75% CI 0.61 to 1.65), 36% and 39% for influenza B/Victoria with a relative risk of 0.91 (98.75% CI 0.50 to 1.66), and 27% and 20% for influenza B/Yamagata with a relative risk of 1.33 (98.75% CI 0.58 to 3.08) and p > 0.0125 for all comparisons.
In the safety evaluation, adjuvanted dose vaccination was associated with a higher frequency of grade 1 local adverse events (predominantly pain) than standard dose vaccination after the first dose (33% versus 13%) and after the second dose (20% versus 8%).
The authors commented that their study highlights the limited benefit of augmented vaccination strategies in the current treatment era for haematologic malignancies. Adjuvanted QIV was not associated with greater immunogenicity than standard dose QIV, and immunogenicity was not improved by a second QIV dose. These findings contrast with those of studies that have shown benefit with two doses of high-dose QIV and the H1N1/09 adjuvanted vaccine formulation in patients after allogeneic HCT.
Immunogenicity remains suboptimal in patients with CLL or non-Hodgkin’s lymphoma, who represent a priority population for other preventive strategies. Regardless of vaccination strategy, the percentage of participants with seroconversion was particularly lower among those with CLL or non-Hodgkin’s lymphoma (5-30%) than among those with multiple myeloma (40-81%), probably related to their B-cell depleting treatment regimens.
The study was supported by an investigator-initiated research grant from Seqirus.
Reference
Hall VG, Smibert OC, Sullivan SG, et al. Influenza Vaccination Strategies in Patients with Hematologic Cancer. N Engl J Med 2025;392:306-308.