Immunogenicity and Safety of One Dose of Influenza A H1N1v 2009 Adjuvanted Vaccine for Unpreviously Treated Patients with Binet-Stage A Chronic Lymphoid Leukaemia of B-Cell Type (B-CLL): Result of a Prospective Study Conducted In 9 French Centers by the Intergroupe Français GOELAMS/GFLLC-MW

Abstract 3600

In the context of the French Health policy for the 2009 A/H1N1 influenza pandemic, we plan to prospectively vaccinate a cohort of unpreviously treated patients having Binet-stage A B-CLL, with one dose of the AS03- adjuvanted 2009 A/H1N1 vaccine (Pandemrix®, GSK). Safety and humoral and cellular immunogenicity were analyzed. This prospective study was undertaken in 9 centers in France. After signed informed consent form, 64 patients (median age 66 years) were included, with monitoring specific antibodies and biological parameters at Days 0, 21 and Months 2,6 and 12 after vaccination. The primary endpoint was Haemagglutination-Inhibition (HI) response against vaccine antigen: HI seroconversion rates, HI seroprotection rates, Geometric Mean antibody Titers (GMT) and GMT ratio. Preliminary results concern the first 49 evaluable patients compared to healthy adults results (clinical trial D-Pan H1N1-008).

Before vaccination, 14% of the patients had vaccine HI titres > or = 1:40. By day 21 after the vaccination, seroprotection rates were significantly lower than in the healthy population between 60–70 years (65% vs 88%). Only 47% of the patients who presented a seroconversion (GMT= 36 at 21 days post vaccination). So, quantitatively (seroconversion rate) and qualitatively (GMT corresponding to antibody production efficacy), the serological immune response was reduced compared to healthy subjects. Based on accepted immunological surrogates, these preliminary data suggest that one dose of A/H1N1 adjuvanted vaccine leads to protect only less than 50% of patients with untreated B-CLL as compared to 88% for healthy adults between 60–70 years. The vaccine was well tolerated without any serious adverse event. Solicited injection site and general symptoms were reported, but they were transient and mainly mild to moderate. In addition, no significant variation was observed on tumour cell levels in peripheral blood. Only a slight increase of CD8 cells was seen at 2 months. No variation on immunoglobulin (Ig) dosage including IgM levels. In addition, new results concerning predictive surrogate markers, seroprotection rates at 6 and 12 months after vaccination, A/H1N1 specific memory B cell production, their in vitro reactivation and specific response (ELI-spot) will be presented. In conclusion, 1 dose of A/H1N1 vaccine protects around 50% of untreated patients with B-CLL. So, it could be interesting to test 2 doses of injections for this population in order to increase antibody production capacity and this will be the recommendation for such patients, particularly with B-cell malignancy.