Immunogenicity, safety, and tolerability of 13-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal polysaccharide vaccine in recipients of allogeneic hematopoietic stem cell transplant aged ≥2 years: an open-label study

Catherine Cordonnier, Per Ljungman, Christine Juergens, Johan Maertens, Dominik Selleslag, Vani Sundaraiyer, Peter C Giardina, Keri Clarke, William C Gruber, Daniel A Scott, Beate Schmoele-Thoma, 3003 Study Group, Catherine Cordonnier, Per Ljungman, Christine Juergens, Johan Maertens, Dominik Selleslag, Vani Sundaraiyer, Peter C Giardina, Keri Clarke, William C Gruber, Daniel A Scott, Beate Schmoele-Thoma, 3003 Study Group

Abstract

Background: Life-threatening Streptococcus pneumoniae infections often occur after hematopoietic stem cell transplant (HSCT); vaccination is important for prevention.

Methods: In an open-label study, patients (n = 251) 3-6 months after allogeneic HSCT received 3 doses of 13-valent pneumococcal conjugate vaccine (PCV13) at 1-month intervals, a fourth dose 6 months later, and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) 1 month later. Immunogenicity at prespecified time points and vaccine safety were assessed.

Results: In the evaluable immunogenicity population (N = 216; mean age, 37.8 years), geometric mean fold rises (GMFRs) of immunoglobulin G geometric mean concentrations from baseline to postdose 3 showed significant increases in antibody levels across all PCV13 serotypes (GMFR range, 2.99-23.85; 95% confidence interval lower limit, >1); there were significant declines over the next 6 months, significant increases from predose 4 to postdose 4 (GMFR range, 3.00-6.97), and little change after PPSV23 (GMFR range, 0.86-1.12). Local and systemic reactions were more frequent after dose 4. Six patients experienced serious adverse events possibly related to PCV13 (facial diplegia, injection-site erythema and pyrexia, autoimmune hemolytic anemia, and suspected lack of vaccine efficacy after dose 3 leading to pneumococcal infection), PCV13 and PPSV23 (Guillain-Barré syndrome), or PPSV23 (cellulitis). There were 14 deaths, none related to study vaccines.

Conclusions: A 3-dose PCV13 regimen followed by a booster dose may be required to protect against pneumococcal disease in HSCT recipients. Dose 4 was associated with increased local and systemic reactions, but the overall safety profile of a 4-dose regimen was considered acceptable.

Clinical trials registration: NCT00980655.

Keywords: 13-valent pneumococcal conjugate vaccine; 23-valent pneumococcal polysaccharide vaccine; Streptococcus pneumoniae infections; hematopoietic stem cell transplant.

© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Patient disposition. The term “prohibited medication” refers to predefined medication that excluded patients from the evaluable immunogenicity population: immunoglobulins (n = 18), rituximab (n = 4), both rituximab and immunoglobulins (n = 1), and donor lymphocyte infusions (n = 1). Abbreviations: AE, adverse event; GVHD, graft-vs-host disease; HSCT, hematopoietic stem cell transplant; PCV13, 13-valent pneumococcal conjugate vaccine; PPSV23, 23-valent pneumococcal polysaccharide vaccine.
Figure 2.
Figure 2.
Pneumococcal immunoglobulin G (IgG) geometric mean concentrations (GMCs) in the evaluable immunogenicity population after 3 doses of 13-valent pneumococcal conjugate vaccine (monthly), a booster dose (6 months later), and a dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) (1 month later).

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