A prospective study of the factors shaping antibody responses to the AS03-adjuvanted influenza A/H1N1 vaccine in cancer outpatients

Abstract

Purpose: To identify the determinants of antibody responses to adjuvanted influenza A/H1N1/09 vaccines in a cohort of cancer outpatients.

Patients and methods: Patients with cancer and controls were enrolled in a prospective single-center field study. Two doses of AS03-adjuvanted pandemic influenza vaccine were administered to patients and one dose was administered to controls. Antibody responses were measured using hemagglutination inhibition and confirmed by microneutralization. Geometric mean titers (GMTs) and seroprotection rates (defined as GMTs ≥40) were compared.

Results: Immunizations were safe and well tolerated in 197 cancer patients (lymphoma, 57; glioma, 26; lung or head and neck, 37; gastrointestinal, 41; breast, 36) and 138 controls. Similar seroprotection rates (82.3% versus 87%) and GMTs (336.9 versus 329.9) were achieved after two doses of adjuvanted vaccine in cancer patients and one dose in controls. Univariate analyses identified older age, prior immunization against seasonal influenza, lymphoma, CD4 count, active chemotherapy, and rituximab and steroid treatments as being associated with weaker antibody responses. However, only age and chemotherapy plus rituximab remained independent determinants of vaccine responses in multivariate analyses.

Conclusions: Two doses of AS03-adjuvanted influenza vaccine elicited potent antibody responses in most cancer patients despite ongoing chemotherapy, with the exception of rituximab-induced B-cell depletion. Oncology patients treated in an outpatient setting benefit from preventive vaccination against influenza with adjuvanted vaccines.

Figure 1.

Reverse cumulative distribution of anti–influenza A/H1N1 antibodies in cancer patients and controls. Blood was collected prior to immunization and 3–4 weeks after one (controls and 19 patients) or two (181 patients) vaccine doses. The curves represent the distribution of individual antibody levels measured by a hemagglutination inhibition (HAI) assay. The vertical dotted line represents the 1:40 seroprotective threshold.

Figure 2.

Reverse cumulative distribution of anti–influenza A/H1N1 antibody titers in patients with different cancer types and controls, before and after immunization. Blood was collected as described in Figure 1 caption. The curves represent the distribution of individual antibody levels measured by a hemagglutination inhibition (HAI) assay. The vertical dotted line represents the 1:40 seroprotective threshold.