Dr. .... ....... | DD.MM.YYYY
A 4-year-old boy underwent bone marrow transplantation one year ago as part of metastatic mesoblastic nephroma treatment, today he receives Elortinib therapy. According to his post-transplantation vaccination plan he needs to be vaccinated with the PPSV23 vaccine, but in immunosuppressed\GVHD patients, PPSV23 vaccination is delayed, and PCV13 vaccine is given instead (as a result of possible weak immune response to the PPSV23 vaccine)
What is the currently available data regarding PPSV23 immunogenicity in patients receiving Elortinib therapy?
The findings of our research show that there is a lack of data regarding the PPSV23 vaccine immunogenicity in patients receiving Erlotinib. For this reason, we choose to provide current evidence about the combination of this vaccine in iatrogenic immunosuppressant patients, with a focus on post Hematopoietic stem cell transplant and other Tyrosine kinase inhibitors.
The research results show that immunosuppressors and Tyrosine kinase inhibitors specifically, reduce PPSV23 vaccine immunogenicity. However, according to the literature, it is still recommended to give it to post-HSCT patients treated with immunosuppressors, because there are mixed results in the literature regarding its contribution to elevating antibodies against Streptococcus pneumoniae strains that are not covered by PCV13.
As a result, we suggest that the vaccination plan described in the article published in the American Journal of Hematology (4 PCV13 shots followed by one PPSV23) should also be considered for your patient.
Neither the services nor the research report constitute medical advice of any kind and are not intended to be a substitute for professional medical advice.
Meta Medical Findings
- Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7) – The current European Vaccination of Haematopoietic Stem Cell Transplant Recipients Guidelines1, published in 2019 in The Lancet Infectious Diseases (Q1, Impact Factor 15.6 ), provides an update on vaccination of all patients with hematological malignancies, including HSCT recipients:
According to the guidelines, PPSV23 should be given to pediatric patients in the same schedule as recommended for adults, and under immunosuppressors, 1 dose of PPSV23 should be given, not earlier than 8 weeks after the last PCV.
Those recommendations are also supported by the 2013 IDSA Clinical Practice2 Guideline for Vaccination of the Immunocompromised Host published in 2014 in Clinical Infectious Diseases journal and by the recommendations3 of the Advisory Committee on Immunization Practices (ACIP) published in 2013 in Morbidity and Mortality Weekly Report.
- Immunogenicity of a 5-dose pneumococcal vaccination schedule following allogeneic hematopoietic stem cell transplantation – An article4 published in the American Journal of Hematology (Q1, Impact Factor 6.5) in 2022 reviewed the Immunogenicity of a 5-dose pneumococcal vaccination schedule following allogeneic hematopoietic stem cell transplantation:
The study population included 89 adults (median age 54), of which 52 (58%) used immunosuppressive therapy at baseline, 37 (43%) used it at 8-month follow-up, and IgG levels were measured for all vaccine serotypes by immunoassay. The primary outcome was overall seroprotection at T12 defined as an IgG concentration ≥1.3 μg/ml for 17/24 vaccine serotypes in HCST recipients with and without immunosuppressive therapy at baseline.
The results show that overall seroprotection was 24% (11/46) for patients with immunosuppressive therapy at baseline (p = .03), and it was higher for PCV13 serotypes (54%; p = .03) and lower for PPSV23-unique serotypes (13%; p = .1 – not significant). IgG concentrations increased significantly over time for all 24 serotypes.
According to the researchers, seroprotection rates and IgG levels against serotypes 8, 9N, 10A, and 22F (all exclusive to PPSV23), currently in the top 10 of most common serotypes causing IPD,6-8 increased significantly in both patients with and without immunosuppressive therapy, with acceptable seroprotection rates for several of these common serotypes. In addition, no significant difference in the protection rates for PPSV23-unique serotypes between patients with and without immunosuppressive therapy was observed. As a result, the researchers recommend that PPSV23 should be administered to all HSCT recipients regardless of the use of immunosuppressive agents/GvHD.
In addition, a possible limitation of this study for the adult population can help base the recommendation mentioned above on children. The researchers used a conservative correlation of protection of ≥1.3 μg/ml for 70% of serotypes proposed by the American Association of Allergy Asthma and Immunology (AAAAI), which was meant to reflect real-life protection for adults. On the contrary, WHO cut-off (≥0.35 μg/ml) is based on clinical studies in children using PCV7, so it is reasonable to assume that the data in the study can underestimate the real seroprotection rates in children.
- Chronic Myeloid Leukemia in Children: Immune Function and Vaccinations – An article5 published in the Journal of Clinical Medicine (Q1, Impact Factor 4.8) in 2021 reviews the immune function and vaccinations of Chronic Myeloid Leukemia ill children, with a focus on the influence of Tyrosine kinase inhibitors. According to the writers, It has been demonstrated that TKIs impair B-cell responses through off-target inhibition of the kinases involved in cell signaling, as mentioned in research of adult patients with CML on TKIs, which achieved lower pneumococcal IgG and IgM titer responses (75% versus 100% in the healthy controls) after vaccination with PPSV23.
In addition, the immunogenicity of pneumococcal conjugate vaccines (PCVs) is higher than PPSV23 because of the T-cell-dependent response induced by the conjugation with the diphtheria protein. While there is no data on PCV in patients with CML, one may reasonably deduce from data in other immunocompromised populations to recommend one dose of PCV, followed at least 2 months later by one dose of PPSV23.
- Casting a wider protective net: Anti-infective vaccine strategies for patients with hematologic malignancy and blood and marrow transplantation – An article6 published in Blood Reviews journal (Q1, Impact Factor 10.1)in 2021 presents vaccine strategies for patients with hematologic malignancy and blood and marrow transplantation. Concerning Streptococcus pneumonia vaccination after HCT, the researchers mention a large international multicenter study to evaluate the safety and efficacy of serial doses of PCV13 starting six months after HCT followed by a dose of PPSV23.
According to the researchers, the current NCCN guidelines recommend three doses of PCV13 followed by a dose of PPSV23. The study mentioned above added a 4th PCV13 dose given one month apart and a fourth administered six months later, followed by PPSV23 a month after the 4th PCV13 vaccination. These 4 initial doses elicited a similar immune response as one PCV13 dose in healthy subjects and found no additional immunogenicity after the PPSV23 vaccine.
In addition, the article presents the results of an Australian study that retrospectively evaluated over 800 HCT recipients who either received PPSV23 vaccine or PCV13 as a standard of care. They found successful pneumococcal vaccination rates of over 90% but the invasive pneumococcal disease was more likely in subjects who received PPSV23 (38.5/1000) rather than PCV13 (4.0/1000).
- Immunogenicity of the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Followed by the 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23) in Adults with and without Immunosuppressive Therapy – An article7 published in Vaccines journal (Q2, Impact Factor 4.9) in 2022 presented the immunogenicity of the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) followed by the 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23) in 214 adults with and without immunosuppressive therapy. The primary outcome was seroprotection, defined as the proportion of patients with a postimmunization IgG concentration of ≥1.3 µg/mL for at least 70% (17/24) of the serotypes of PCV13 + PPSV23.
The study result shows that in all vaccine serotypes, IgG levels increased significantly in both treatment subgroups and controls, with peak seroprotection rates of 44% (combination therapy), 58% (conventional immunomodulators), 57% (biological immunomodulators), and 82% (controls). By month 12, seroprotection had decreased to 24%, 48%, 39%, and 63%, respectively. Although pneumococcal vaccination with PCV13 + PPSV23 was immunogenic in all treatment groups, impaired vaccination responses were observed in patients using immunosuppressive medication.
The effect of immunosuppressive agents on immunogenicity of pneumococcal vaccination: A systematic review and meta-analysis – A meta-analysis8 published in Vaccine (Q1, Impact Factor 3.8) journal in 2018 presents the effect of immunosuppressive agents on the immunogenicity of pneumococcal vaccination in 764 adult patients with autoimmune diseases using immunosuppressive drugs (MTX, DMARDs, TNFa, Rituximab). According to the results, the response rate was 26% for PCV and 37% for PPSV23.
- Cordonnier C, Einarsdottir S, Cesaro S, et al. Vaccination of haemopoietic stem cell transplant recipients: guidelines of the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis. 2019;19(6):e200-e212. doi:10.1016/S1473-3099(18)30600-5
- Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host [published correction appears in Clin Infect Dis. 2014 Jul 1;59(1):144]. Clin Infect Dis. 2014;58(3):e44-e100. doi:10.1093/cid/cit684
- Centers for Disease Control and Prevention (CDC). Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among children aged 6-18 years with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2013;62(25):521-524.
- Garcia Garrido HM, Haggenburg S, Schoordijk MCE, et al. Immunogenicity of a 5-dose pneumococcal vaccination schedule following allogeneic hematopoietic stem cell transplantation. Am J Hematol. 2022;97(5):592-602. doi:10.1002/ajh.26493
- Suttorp M, Webster Carrion A, Hijiya N. Chronic Myeloid Leukemia in Children: Immune Function and Vaccinations. J Clin Med. 2021;10(18):4056. Published 2021 Sep 8. doi:10.3390/jcm10184056
- McMasters M, Blair BM, Lazarus HM, Alonso CD. Casting a wider protective net: Anti-infective vaccine strategies for patients with hematologic malignancy and blood and marrow transplantation. Blood Rev. 2021;47:100779. doi:10.1016/j.blre.2020.100779
- Garcia Garrido HM, Vollaard A, D’Haens GR, et al. Immunogenicity of the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Followed by the 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV23) in Adults with and without Immunosuppressive Therapy. Vaccines (Basel). 2022;10(5):795. Published 2022 May 17. doi:10.3390/vaccines10050795
- van Aalst M, Langedijk AC, Spijker R, de Bree GJ, Grobusch MP, Goorhuis A. The effect of immunosuppressive agents on immunogenicity of pneumococcal vaccination: A systematic review and meta-analysis. Vaccine. 2018;36(39):5832-5845. doi:10.1016/j.vaccine.2018.07.039