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CONJUGATED PNEUMOCOCCAL VACCINE TRIGGERS A BETTER IMMUNE RESPONSE THAN POLYSACCHARIDE PNEUMOCOCCAL VACCINE IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIAA RANDOMIZED STUDY BY THE SWEDISH CLL GROUP
Author(s): ,
Tobias Svensson
Affiliations:
Section of Heamatology,Institution of Medical Sciences,Uppsala,Sweden
,
Magdalena Kättström
Affiliations:
Department of Medical Sciences, Örebro University Hospital,Örebro,Sweden
,
Ylva Hammarlund
Affiliations:
Falun Hospital,Falun,Sweden
,
Daniel Roth
Affiliations:
Institution of Clinical Sciences, Faculty of Medicine, Lund University Hospital,Lund,Sweden
,
Per-Ola Andersson
Affiliations:
Hematology and Coagulation Section, Sahlgrenska University Hospital,Göteborg,Sweden
,
Magnus Svensson
Affiliations:
Eskilstuna Hospital,Eskilstuna,Sweden
,
Ingmar Nilsson
Affiliations:
Karlstad Hospital,Karlstad,Sweden
,
Lars Rombo
Affiliations:
Eskilstuna Hospital,Eskilstuna,Sweden
,
Honar Cherif
Affiliations:
Section of Haematology,Institution of Medical Sciences,Uppsala,Sweden
Eva Kimby
Affiliations:
Department of Medicine, Unit of Hematology,Karolinska Institute and University Hospital,Huddinge,Sweden
(Abstract release date: 05/18/17) EHA Library. Svensson T. 06/25/17; 182092; S805
Tobias Svensson
Tobias Svensson
Contributions
Abstract

Abstract: S805

Type: Oral Presentation

Presentation during EHA22: On Sunday, June 25, 2017 from 08:15 - 08:30

Location: Room N104

Background
Patients with CLL have an increased risk for infection and Streptococcus pneumoniae is one of the most common pathogens with high morbidity.  Patients with CLL are known to respond poorly to the traditionally used polysaccharide vaccines. Conjugation of polysaccharide to protein carriers renders a thymus-dependent, memory-inducing and more immunogenic vaccine. In patients with CLL, there is no consensus on a recommendation for pneumococcal vaccination, due to a lack of comparative studies.

Aims
To determine if patients with untreated chronic lymphocytic leukemia (CLL) benefit from vaccination with a 13-valent conjugated pneumococcal vaccine (PCV13), Prevenar13®, compared with a 23-valent capsular polysaccharide vaccine (PPSV23), Pneumovax®, in terms of immune response.

Methods
128 treatment naïve CLL patients from eight hematology clinics in Sweden were randomized to vaccination with PCV13 (n=63) or PPSV23 (n=65) after stratification by IgG levels and CLL clinical stage (Rai). Blood samples for evaluation of immune response were obtained at baseline, at one and at six months after vaccination. Analyses for each of the 12 pneumococcal serotypes common for PCV13 and PPSV23 were performed by opsonophagocytic assay (OPA) and enzyme-linked immunosorbent assay (ELISA).

Results
PCV13 elicited a superior immune response than PPSV23 in 10/12 serotypes one month after vaccination and in 5/12 serotypes six months after vaccination, measured as OPA geometric mean titers (GMTs). Geometric mean concentrations of serotype-specific IgG antibodies elicited by PCV13 as measured by ELISA, were higher than those elicited by PPSV23 in half of the common serotypes, both after one and six months. The proportion of patients with good response (defined as response in 8 of 12 common serotypes according to predefined response criteria) was higher in PCV13 recipients than in PPSV23 recipients after one month (40% vs. 22%, p=0.034) as well as after six months (33% vs. 17%, p=0.041). Never did PPSV23 trigger a better immune response for any of the serotypes, than PCV13, regardless of analysis. For two of the serotypes, OPA GMTs were lower at the six months than at the one-month follow up. Negative predictive factors for vaccination response were hypogammaglobulinemia and long disease duration. Both vaccines were well tolerated.

Conclusion
In patients with previously untreated CLL, the efficacy of PCV13 in terms of immune response is superior to PPSV23 for many serotypes common for the two vaccines. PCV13 should be considered as a part in vaccination programs against Streptococcus pneumoniae for these patients and administered as early as possible during the course of the disease. 

Session topic: 29. Infectious diseases, supportive care

Keyword(s): Vaccination, Chronic Lymphocytic Leukemia

Abstract: S805

Type: Oral Presentation

Presentation during EHA22: On Sunday, June 25, 2017 from 08:15 - 08:30

Location: Room N104

Background
Patients with CLL have an increased risk for infection and Streptococcus pneumoniae is one of the most common pathogens with high morbidity.  Patients with CLL are known to respond poorly to the traditionally used polysaccharide vaccines. Conjugation of polysaccharide to protein carriers renders a thymus-dependent, memory-inducing and more immunogenic vaccine. In patients with CLL, there is no consensus on a recommendation for pneumococcal vaccination, due to a lack of comparative studies.

Aims
To determine if patients with untreated chronic lymphocytic leukemia (CLL) benefit from vaccination with a 13-valent conjugated pneumococcal vaccine (PCV13), Prevenar13®, compared with a 23-valent capsular polysaccharide vaccine (PPSV23), Pneumovax®, in terms of immune response.

Methods
128 treatment naïve CLL patients from eight hematology clinics in Sweden were randomized to vaccination with PCV13 (n=63) or PPSV23 (n=65) after stratification by IgG levels and CLL clinical stage (Rai). Blood samples for evaluation of immune response were obtained at baseline, at one and at six months after vaccination. Analyses for each of the 12 pneumococcal serotypes common for PCV13 and PPSV23 were performed by opsonophagocytic assay (OPA) and enzyme-linked immunosorbent assay (ELISA).

Results
PCV13 elicited a superior immune response than PPSV23 in 10/12 serotypes one month after vaccination and in 5/12 serotypes six months after vaccination, measured as OPA geometric mean titers (GMTs). Geometric mean concentrations of serotype-specific IgG antibodies elicited by PCV13 as measured by ELISA, were higher than those elicited by PPSV23 in half of the common serotypes, both after one and six months. The proportion of patients with good response (defined as response in 8 of 12 common serotypes according to predefined response criteria) was higher in PCV13 recipients than in PPSV23 recipients after one month (40% vs. 22%, p=0.034) as well as after six months (33% vs. 17%, p=0.041). Never did PPSV23 trigger a better immune response for any of the serotypes, than PCV13, regardless of analysis. For two of the serotypes, OPA GMTs were lower at the six months than at the one-month follow up. Negative predictive factors for vaccination response were hypogammaglobulinemia and long disease duration. Both vaccines were well tolerated.

Conclusion
In patients with previously untreated CLL, the efficacy of PCV13 in terms of immune response is superior to PPSV23 for many serotypes common for the two vaccines. PCV13 should be considered as a part in vaccination programs against Streptococcus pneumoniae for these patients and administered as early as possible during the course of the disease. 

Session topic: 29. Infectious diseases, supportive care

Keyword(s): Vaccination, Chronic Lymphocytic Leukemia

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