P1523: immunogenicity of the 13-valent pneumococcal conjugated vaccine followed by the 23-valent polysaccharide vaccine in chronic lymphocytic leukemia

Topic: 30. Infections in hematology (incl. supportive care/therapy) Background: Patients with Chronic Lymphocytic Leukemia (CLL) have a 36-fold increased risk of invasive pneumococcal disease (IPD) compared to healthy adults. Therefore, most guidelines recommend vaccination with Prevenar13®, a 13-valent pneumococcal conjugated vaccine (PCV13) followed 2 months later by Pneumovax23®, a 23-valent polysaccharide vaccine (PPSV23). While CLL as well as immunosuppressive treatment have been identified as major determinants of vaccination-induced immunogenicity, knowledge about the immunogenicity of this sequential pneumococcal vaccination schedule in CLL patients is lacking. Aims: To assess the immunogenicity of the sequential vaccination schedule of PCV13 followed by PPSV23 in treatment naive and treated CLL patients. Methods: We quantified pneumococcal immunoglobulin G (IgG) antibody concentrations against 5 pneumococcal serotypes shared across both vaccines (6B, 9V, 14, 19F, 23F), and against 4 serotypes unique to PPSV23 (8, 15B, 20, 33F), prior to and 4-8 weeks after vaccination using a validated multiplex immunoassay, Luminex®. The primary outcome was the serologic response rate, defined as a ≥4-fold increase in ≥70% of the serotype-specific anti-pneumococcal IgG antibodies. Secondary outcome was serologic protection, defined as an antibody concentration of ≥1.3 mcg/ml for ≥70% of all measured serotypes. Results: In this retrospective cohort study, we included 143 CLL patients, either treated (n=38) or naive to treatment (n=105), who previously completed the vaccination and measurement schedule. Median time since CLL diagnosis was 3.6 years. While serotype-specific antibody concentrations increased significantly after vaccination, the overall serologic response rate of 10.5% was low, and significantly influenced by treatment status and prior lymphocyte count. The serotype-specific pneumococcal IgG antibody concentrations after vaccination were all significantly lower in treated than in previously untreated patients. The serologic protection rate was obtained in 13% of untreated and 3% of treated CLL patients. Summary/Conclusion: Despite this poor immunogenicity in CLL patients, vaccination is still recommended, because the high incidence of IPD in this population probably offsets the lower serologic response, but research should focus on vaccine regimens with a higher immunogenic potential, such as multi-dose schedules with higher-valent T cell dependent conjugate vaccines. Keywords: Infection, Vaccination, Chronic lymphocytic leukemia, Immunodeficiency