ABSTRACT: Influenza infection is a potential cause of additional morbidity and mortality in patients who are immunocompromised because of cancer or its treatment. Of particular note, influenza infection may delay or interrupt chemotherapy and necessitate hospitalization. Successful immunization depends on an intact immune system that can produce antibodies in response to antigen exposure. Patients with cancer often have a suppressed immune system, resulting from their disease and/or immunosuppressive therapies, and as a consequence they may have a suboptimal serologic response to influenza vaccination. Since vaccination is the only proven method for preventing influenza infection, the Advisory Committee on Immunization Practices recommends seasonal influenza vaccination for adults without contraindications who have disease- or medication-related immunosuppression. Patients with cancer should be given the trivalent inactivated vaccine. Preliminary data suggest that administering the vaccine between cycles of chemotherapy may yield the best results.
Yearly influenza vaccination is the most effective way to prevent influenza infection and its complications. The efficacy of influenza vaccination in patients with cancer has not been well studied in general, and in patients with solid tumor malignancies in particular. The optimal timing for administration of the influenza vaccine in patients with cancer who are receiving chemotherapy is not clear. This review highlights the burden of influenza in patients with cancer, the response to influenza immunization in this patient population, and vaccination recommendations.
Influenza A viruses are negatively-stranded RNA viruses with eight segmented RNA components in the genome. Two of the proteins coded by the genome are glycosylated proteins on the cell surface—hemagglutinin (H) and neuraminidase (N)—that facilitate viral attachment and release from the cells of the host, as well as determining how the virus strains are named (eg, H1N1, H3N2; the numbers refer to the subtypes of the H and N antigens). The virus is capable of genetic variability as a result of two features. First, its segmented genome allows reassortment of genetic material, which explains why the H1N1 virus contains genetic material from pigs, humans, and birds. Second, inefficient proofreading during viral RNA replication causes transcription errors and amino acid substitutions in H and N; this results in new variants that can evade pre-existing immunity and thus cause epidemics.
Circulating human influenza viruses are subject to antigenic shifts that require annual adaptation of the vaccine formulation. The vaccine is adapted to help ensure the closest match between circulating strains and those found in the vaccine. In the past, there have been monovalent and bivalent vaccines. Since 1977, however, trivalent vaccines, which contain influenza A virus subtypes H1N1 and H3N2 and influenza B viruses, have been used.
The rapid global spread of a novel influenza A virus of swine origin (H1N1) prompted the World Health Organization (WHO) to declare a pandemic on June 11, 2009.[5,6] According to data from the Centers for Disease Control and Prevention (CDC), the virus had infected at least 1 million individuals as of August 2009.[6,7] As of October 3, 2009, 99% of circulating influenza viruses in the United States were 2009 H1N1 influenza virus. The trivalent seasonal influenza vaccines in use at the time did not provide protective immunity against the H1N1 virus. Thus, a new vaccine against the H1N1 influenza virus was developed, and this product was approved by the FDA in September 2009.
Vaccines for the 2010-2011 northern hemisphere influenza season contain the following: A/California/7/2009 (H1N1-like virus); A/Perth/16/2009 (H3N2-like virus); and B/Brisbane/60-2008-like antigens. The Table lists the influenza vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) for the 2010-2011 influenza season.
The Burden of Influenza in Cancer Patients
Influenza infection is a potential cause of additional morbidity and mortality in patients who are immunocompromised because of cancer or its treatment. During the Asian influenza epidemics of 1957 to 1966, increased mortality was noted in cancer patients. Of particular note, influenza infection may delay or interrupt chemotherapy and necessitate hospitalization.[10,11]
Active immunization by way of influenza vaccination relies on an intact immune system that can produce antibodies in response to antigen exposure. Persons with cancer, however, often have immune deficiencies as a result of their disease and/or immunosuppressive therapies. Thus, a suboptimal serologic response to influenza vaccination may be seen in this population. However, these high-risk patients are at risk for complications from influenza infection and need to be protected with immunization. Misconceptions among both patients and physicians about the benefits of the vaccine in these patients, including concerns about safety and side-effect profiles, may hinder timely administration of the vaccine.
CDC Recommendations for Influenza Vaccination
The ACIP provides annual recommendations for use of the influenza vaccine. This year, the ACIP recommends seasonal influenza vaccination for adults without contraindications who have disease- or medication-related immunosuppression. Patients with hematologic and solid malignancies are considered to be functionally immunosuppressed secondary to their disease and/or treatment and should be given the trivalent inactivated vaccine.
Assessing Response to Influenza Vaccination
In the FDA’s “Guidance for Industry” document regarding inactivated influenza vaccines, results of hemagglutination (HI) assays are considered appropriate for assessing immunogenicity. HI assays provide a standardized method for comparing serologic responses to various vaccines. The basis of the HI assay is that antibodies to influenza virus prevent virus attachment to red blood cells. Hemagglutination is therefore inhibited when antibodies are present. Post-vaccination HI antibody titers of 1:40 or greater, or a four-fold rise in titers from those measured before vaccination, is indicative of protective immunity. Studies have also shown that these same HI titers correspond with a 50% decreased risk of active influenza infection in patients.
Prospective studies in healthy persons demonstrate the inactivated influenza vaccine to have an efficacy of 70% to 90% for the prevention of influenza. A question frequently asked by patients receiving chemotherapy is whether they will benefit from vaccination against influenza.