1154 - Impaired long-term antibody persistence after primary immunization with pneumococcal vaccines in patients with chronic lymphocytic leukemia compared to immunocompetent controls

Background: Patients with chronic lymphocytic leukemia (CLL) have an increased risk of invasive pneumococcal disease (IPD). Impaired immune response to pneumococcal vaccination calls for improved vaccination strategies. In a previous randomized study of treatment-naïve CLL patients (Svensson et. al. Vaccine, 2018), we showed that a T-cell dependent conjugated pneumococcal vaccine (PCV13) induced a superior immune response compared to non-T cell dependent polysaccharide vaccine (PPSV23), estimated both by enzyme-linked immunosorbent assay for IgG titers and opsonophagocytic assay (OPA) for antibody functionality. Follow-up studies of long-term pneumococcal antibody persistence in CLL patients after PCV13 and PPSV23 are lacking, and there are no recommendations on revaccination strategies.

Aim: To assess the long-term antibody persistence after primary immunization with PCV13 or PPSV23 in CLL patients and healthy controls, and the response to revaccination with PCV13 + PPSV23 or PCV13 + PCV13.

Method: Seventy-four CLL patients from our previous study were included 4-6 years after primary immunization with PCV13 (Group A, n=36) or PPSV23 (Group B, n=38). In addition, thirty-one immunocompetent controls were recruited, primary immunized with PCV13 (Group C, n=9) or PPSV23 (Group D, n=22) 3-7 years previously. The CLL patients and controls were assessed for antibody persistence and then revaccinated with PCV13. After 8 weeks, the CLL patients received a second revaccination with either PPSV23 (Group A) or PCV13 (Group B), but the controls received no further vaccine. Serum samples were collected before and 8 weeks after first revaccination, 8 weeks after second revaccination and after 12, 18, 24 and 30 months. A bead-based multiplex immunoassay was used for quantitation of IgG (µg/mL) against PCV13-related serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F). Rates of serotype-specific IgG levels ≥0.35 µg/mL for >50% (7-13/13) of the serotypes were calculated in CLL patients and controls and used to evaluate persistent antibody levels.

Results: After a median time of 5 years after primary immunization, the rate of persistent antibody levels in CLL patients were lower compared to controls (29/74, 39% versus 26/31, 84%; p<0.001). No significant difference in rates of persistent antibody levels was seen after primary immunization with PCV13 or PPSV23 in CLL patients (44% vs 34%, p=NS) or controls (89% vs 82%, p=NS), see Table 1. Median time from primary immunization was similar between the four groups (Group A, 65; B, 65.5; C, 60.5; D, 60 months). Median time from CLL diagnosis to revaccination in group A and B were 91 and 85 months, respectively, and hypogammaglobulinemia was seen in 19/74 (26%) CLL patients. Fifty-eight patients (78%) were still treatment-naïve, 9 (12%) were off treatment in remission and 6 (8%) had ongoing treatment with BTK inhibitors or anti-CD20 antibodies.

Conclusion: CLL patients have impaired long-term antibody persistence 5 years after primary immunization with pneumococcal vaccines compared to immunocompetent controls. Whether CLL patients will benefit from pneumococcal revaccinations is currently being analyzed.