Efficacy of single versus boost vaccination against influenza virus in patients with multiple myeloma.

Influenza infection can cause severe complications in patients with multiple myeloma. There are no systematic studies on the efficacy of influenza vaccines in patients with MM. In a retrospective, single-center study we assessed the immune response of MM patients to one and two doses of a trivalent influenza vaccine. The secondary aim of the study was to correlate the immune responses with disease-specific parameters and anti-neoplastic treatment. While a single dose of influenza vaccine resulted in seroprotection in 14.6% of MM patients, the frequency of protective titers was more than doubled (31.3%) after a second dose of the vaccine. There is increasing evidence that the immune response to influenza vaccine in MM patients is mostly insufficient. Protection against influenza is mediated by virus-specific antibodies and depends on the humoral immune response, which is impaired in patients with MM. Preliminary data support the assumption that the immune response can be improved by a second dose of vaccine. During the season 2012/13, MM patients were offered the seasonal influenza vaccination [(Optaflu, Novartis, Basel, Switzerland; a trivalent cell-culture-based influenza vaccine, containing inactivated viral surface antigens of influenza A(H1N1)pdm09, influenza A(H3N2), and influenza B/Yamagata-lineage; hereafter referred to as A(H1N1), A(H3N2) and B/Yamagata)] in our myeloma outpatient clinic. Blood samples were taken before and 4 weeks after each vaccination. Patients were offered a second dose of vaccine if they responded insufficiently to the first vaccination but had not had any serious side effects. Antibody titers were analyzed using the hemagglutination inhibitory (HI) assay. HI titers <1:10, 1:10 to <1:40 and ≥1:40 were considered as negative, indicating immune memory and protection, respectively. Seroconversion was defined as having occurred in seronegative patients if the titer achieved after vaccination was ≥1:40, and in seropositive patients if the ratio achieved was ≥4-fold. Apart from this intervention, diphtheria and tetanus (DT) immunization titers were determined as recall parameters using enzyme-linked immunoassays. DT titers between 0.1 and 1.0 IU/mL were considered as protective, titers >1 IU/mL as indicating long-term protection. Forty-eight patients with smoldering myeloma and MM stage I or higher who had been vaccinated in our myeloma outpatient clinic during the season 2012/13 were included in this study, which was approved by the Institutional Review Board. The patients’ characteristics are summarized in Table 1. Most of the patients had previously received intensive therapies; only two patients had not been given any chemotherapy before the first vaccination. Seventeen patients were in complete or near complete remission at the time of the first vaccination. Differences of HI titers between two time points (before/after first vaccination, after first/after second vaccination and before first/after second vaccination) were analyzed using the signed-rank Wilcoxon test. Seroconversion and seroprotection rates were analyzed comparing the times before, after first and after second vaccination by pairwise McNemar test. The association between medical history and response to vaccine was examined by means of a Fisher exact test for nominal variables and the Wilcoxon test for continuous variables. The absolute increment in titer due to the first vaccina tion was statistically significant for all three strains (Figure 1A). The seroprotection rates against A(H1N1), A(H3N2), B/Yamagata and against all three viruses (total influenza seroprotection) before/after the first vaccination were 19%