Stringent vaccination of cancer patients: is it that important?
Authors: T. Weber, P. Ljungman
Journal: Annals of Oncology (2018)

Patients receiving anticancer therapy are especially vulnerable to illnesses due to infectious diseases. It is known that antibody titers of vaccination-preventable diseases decrease after intensive anticancer treatment [1.Kwon H.J. Lee J.W. Chung N.G. et al.Assessment of serologic immunity to diphtheria-tetanus-pertussis after treatment of Korean pediatric hematology and oncology patients.J Korean Med Sci. 2012; : 78-83Crossref PubMed Scopus (19) Google Scholar] especially in children and in patients undergoing hematopoietic stem-cell transplantation [2.Nilsson A. De Milito A. Engstrom P. et al.Current chemotherapy protocols for childhood acute lymphoblastic leukemia induce loss of humoral immunity to viral vaccination antigens.Pediatrics. 2002; 109: e91Crossref PubMed Scopus (102) Google Scholar, 3.Ljungman P. Lewensohn-Fuchs I. Hammarstrom V. et al.Long-term immunity to measles, mumps, and rubella after allogeneic bone marrow transplantation.Blood. 1994; 84: 657-663Crossref PubMed Google Scholar, 4.Ljungman P. Wiklund H.M. Duraj V. et al.Response to tetanus toxoid immunization after allogeneic bone marrow transplantation.J Infect Dis. 1990; 162: 496-500Crossref PubMed Scopus (112) Google Scholar]. In these patients, vaccinations might help to reduce morbidity and mortality due to vaccination-preventable illnesses by reducing the rates and severity of infections and by minimizing interruptions of anticancer treatment. However, vaccination rates in cancer patients and cancer survivors are unacceptable low [5.Delacruz W. Terrazzino S. Osswald M. et al.Implementing a multidisciplinary approach to enhance compliance with guideline-recommended prechemotherapy pneumococcal vaccination in a military-based medical oncology practice.JOP. 2017; 13: e966-e971Crossref PubMed Scopus (4) Google Scholar, 6.Poeppl W. Lagler H. Raderer M. et al.Influenza vaccination perception and coverage among patients with malignant disease.Vaccine. 2015; 33: 1682-1687Crossref PubMed Scopus (29) Google Scholar, 7.Locher J.L. Rucks A.C. Spencer S.A. et al.Influenza immunization in older adults with and without cancer.J Am Geriatr Soc. 2012; 60: 2099-2103Crossref PubMed Scopus (11) Google Scholar, 8.Underwood J.M. Townsend J.S. Stewart S.L. et al.Surveillance of demographic characteristics and health behaviors among adult cancer survivors–Behavioral Risk Factor Surveillance System, United States, 2009.MMWR Surveill Summ. 2012; 61: 1-23PubMed Google Scholar] and international guidelines are poorly followed [9.Ariza-Heredia E.J. Gulbis A.M. Stolar K.R. et al.Vaccination guidelines after hematopoietic stem cell transplantation: practitioners' knowledge, attitudes, and gap between guidelines and clinical practice.Transpl Infect Dis. 2014; 16: 878-886Crossref PubMed Scopus (29) Google Scholar]. This is in part due to their physicians concerns about the safety and efficacy of vaccines in cancer patients. The plethora of different diseases and treatments as well as type and timing of vaccination during treatment enhance these uncertainties. Moreover, some physicians have concerns to influence the underlying malignant disease negatively [6.Poeppl W. Lagler H. Raderer M. et al.Influenza vaccination perception and coverage among patients with malignant disease.Vaccine. 2015; 33: 1682-1687Crossref PubMed Scopus (29) Google Scholar]. Indeed, sound data for efficacy for most of the vaccinations in patients with cancer are lacking since the size of the population needed to prove clinical efficacy makes it for most vaccine very difficult to study. Pre-licensure studies of vaccines often exclude cancer patients. Post-licensure studies in cancer patients include only a small number of patients. This is not only relevant for assessment of efficacy but it is especially relevant regarding safety data [10.Institute of Medicine Committee to Review Adverse Effects of Vaccines.in: Stratton K. Ford A. Rusch E. Clayton E.W. Adverse Effects of Vaccines: Evidence and Causality. National Academies Press US, Washington DC2011Google Scholar]. There is, however, data on immunological surrogate end points especially in transplant patients. Hence, the use of vaccines in cancer patients is mainly based on the general principles of immunization and on safety data in other cohorts. The vast heterogeneity of malignant diseases and treatments also limit evidence of vaccinations. Different depth and types of immune system dysfunction reflect this heterogeneity. Knowing type and depth of immune system alteration is crucial to assess the risk of severe infections as well as risks and benefits of vaccinations. A patient with breast cancer after surgery, radiation and hormone treatment will be less prone to severe vaccine-preventable infections than a patient treated with high dose chemotherapy for relapsed testicular cancer. Treatments targeting specific components of the immune system, e.g. B-cell depletion by rituximab will lead to far less effective vaccinations especially of sub-unit vaccines with polysaccharides or proteins for at least several months after end of therapy. The existing evidence suggest that correctly applied vaccines in cancer patients have some degree of benefit and do not pose them to excessive harm compared with non-cancer patients. There is no support for safety concerns with inactivated, antigen based or subunit vaccines in patients with cancer or after transplantation different from a healthy population. The situation with live, attenuated vaccines is more of a concern and care should be taken before vaccination with such vaccines. For some vaccines, there are stronger data supporting vaccination to prevent diseases. In a recently updated Cochrane analysis, Bitterman et al. reported a 58% relative reduction of all case mortality by influenza vaccination in patients with solid cancers or hematological malignancies, even if certainty is low [11.Bitterman R. Eliakim-Raz N. Vinograd I. et al.Influenza vaccines in immunosuppressed adults with cancer.Cochrane Database Syst Rev. 2018; 2PubMed Google Scholar]. Similar results were found for patients with cancer and transplant patients [12.Beck C.R. McKenzie B.C. Hashim A.B. Harris R.C. University of Nottingham Influenza and the ImmunoCompromised (UNIIC) Study Group, Nguyen-Van-Tam JS Influenza vaccination for immunocompromised patients: systematic review and meta-analysis by etiology.J Infect Dis. 2012; 206: 1250-1259Crossref PubMed Scopus (81) Google Scholar]. For pneumococcal disease, it was shown that application of the 23-valent pneumococcal polysaccharide vaccine significantly reduces mortality in elderly patients with lung cancer [13.Chiou W.Y. Hung S.K. Lai C.L. et al.Effect of 23-valent pneumococcal polysaccharide vaccine inoculated during anti-cancer treatment period in elderly lung cancer patients on community-acquired pneumonia hospitalization: a Nationwide Population-Based Cohort Study.Medicine (Baltimore). 2015; 94: e1022Crossref PubMed Scopus (19) Google Scholar]. In this issue of Annals of Oncology Rieger et al. report the ‘Anti-infective Vaccination Strategies in Patients with Hematologic Malignancies or Solid Tumors – Guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO)’ [14.Rieger C.T. Liss B. Mellinghoff S. et al.Anti-infective vaccination strategies in patients with hematologic malignancies or solid tumors – guideline of the Infectious Diseases Working Party (AGIHO) of the German Society for Hematology and Medical Oncology (DGHO).Ann Oncol. 2018; 29: 1354-1365Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar]. The guideline provides expert recommendations on vaccinations for many specific patient groups and treatment situations: patients with solid tumors, acute leukemias, other hematological disorders and functional or anatomic asplenia as well as treatments with rituximab, checkpoint inhibitors or autologous stem cell transplantation. It helps to estimate severity of immune dysfunction, and to administer vaccinations safely without posing the patients to risks of live vaccines. However, there are still some unaddressed aspects in the recommendations given. Novel agents exerting new mechanisms of action are being introduced at a rapid rate. They inhibit immune checkpoints, modulate the immune system as lenalidomide or interact with B-cell pathways crucial as PI3K- or BTK-inhibitors. Their immunocompromising potential is not yet completely understood and evidence on safety and efficacy of vaccines for these situations are lacking. Despite these limitations, the reported recommendations along with other guidelines [15.Rubin L.G. Levin M.J. Ljungman P. et al.2013 IDSA clinical practice guideline for vaccination of the immunocompromised host.Clin Infect Dis. 2014; 58: e44-100Crossref PubMed Scopus (879) Google Scholar, 16.National Comprehensive Cancer Network. Prevention and Treatment of Cancer-Related Infections (Version 1.2018). https://www.nccn.org/professionals/physician_gls/pdf/survivorship.pdf (12 April 2018, date last accessed).Google Scholar, 17.National Comprehensive Cancer Network. Survivorship (Version 3.2017). https://www.nccn.org/professionals/physician_gls/pdf/infections.pdf (12 April 2018, date last accessed).Google Scholar] give a sound framework for vaccination in clinical practice. Based on this framework, efficacy and safety of each vaccine should be evaluated on a case-by-case basis for every patient. What can we do in the future to increase vaccination rates and to decrease harm from vaccination-preventable diseases in cancer patients and survivors? First, developing a broader basis of data by randomized and observational studies and registries including specific patient populations and treatment modalities would be important. Secondly, implementation of institutional vaccination management plan in cancer centers [18.Toleman M.S. Herbert K. McCarthy N. Church D.N. Vaccination of chemotherapy patients—effect of guideline implementation.Support Care Cancer. 2016; 24: 2317-2321Crossref PubMed Scopus (11) Google Scholar] and information of health care providers involved in treating cancer patients could help to increase vaccination rates. None declared.