Flu Vaccination in Patients with Cancer: Emerging Trends

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Influenza epidemics occur every year in the United States, typically beginning in the late fall or winter and concluding during the spring.¹ During the 2006—2007 season, influenza circulated at epidemic levels for about 14 weeks and peaked during February, the month most frequently associated with peak activity over the past 31 influenza seasons.^1,2 According to estimates from the Centers for Disease Control and Prevention (CDC), influenza has caused roughly 36,000 deaths and 226,000 hospitalizations annually.^3,4 However, the rate of flu varies each year based on viral virulence and duration of circulation. Complications, hospitalizations, and death are most common in patients aged ≥65 years.^5,6 In recent years, there has been a growing recognition among oncologists and other cancer care professionals of the importance of vaccination against influenza in patients with cancer.

For most people with cancer, vaccination for influenza is not only safe, but also a crucial part of staying as healthy as possible. Owing to their weakened immune system, patients with cancer are at high risk for infection with flu and pneumonia viruses, which can be lethal in these individuals. Yearly flu and pneumonia shots often prevent infection entirely and can lessen the severity of illness in those who do get sick.

Influenza Viruses

Influenza viruses are divided into three types, designated A, B, and C. Influenza types A and B are responsible for epidemics of respiratory illness that occur almost every winter and are often associated with increased rates for hospitalization and death. Influenza type C differs from types A and B in some important ways. Type C infection usually causes either a very mild respiratory illness or no symptoms at all; it does not cause epidemics and does not have the severe public health impact that influenza types A and B do. Efforts to control the impact of influenza are aimed at types A and B.

Influenza type A viruses are divided into subtypes based on differences in two viral proteins called the hemagglutinin (H) and the neuraminidase (N). The current subtypes of influenza A are designated A(H1N1) and A(H3N2). Influenza A(H1N1), A(H3N2), and influenza B strains are included in each year’s influenza vaccine. In the years since its emergence, type A(H3N2) epidemics have caused more than 400,000 deaths in the United States alone, and more than 90% of these deaths have occurred among people age 65 and older.

Influenza type A viruses undergo two kinds of changes. One is a series of mutations that occur over time and cause a gradual change in the virus. This is called antigenic “drift.” This constant changing enables the virus to evade the immune system of its host, so that people are susceptible to influenza virus infection throughout life. This process works as follows: A person infected with influenza virus develops antibody against that virus; as the virus changes, the “older” antibody no longer recognizes the “newer” virus, and reinfection can occur The older antibody can, however, provide partial protection against re-infection.

The other kind of change is an abrupt change in the hemagglutinin and/or the neuraminidase proteins. This is called antigenic “shift.” In this case, a new subtype of the virus suddenly emerges. Type A viruses undergo both kinds of changes; influenza type B viruses change only by the more gradual process of antigenic drift.

CDC Recommendations For Influenza Vaccination

Influenza vaccination is the most effective method for preventing influenza virus infection and its complications, which may be severe. The CDC updated its recommendations regarding who should receive influenza vaccination in 2008.^1,7 Current recommendations regarding annual vaccination in children/adolescents and adults are summarized in Table 1 and Table 2, respectively. It is important to note that patients with cancer may fall into several of the categories shown in the tables.

In 2008, the Advisory Committee on Immunization Practices (ACIP) of the CDC expanded its recommendations for influenza vaccination for school-aged children.^1,7 The ACIP-CDC now recommends that all children aged six months to 18 years receive annual influenza vaccination, beginning in 2008 if feasible, but beginning no later than during the 2009—2010 influenza season.^1,7

Since influenza viruses undergo frequent antigenic change, persons recommended for vaccination must receive an annual vaccination against the viruses known to be in circulation each year.

According to the CDC,¹ trivalent influenza vaccine may be used for any person aged ≥6 months, including those with high-risk conditions. The 2008—2009 trivalent vaccine virus strains are A/Brisbane/59/2007 (H1N1)-like, A/Brisbane/10/2007 (H3N2)-like, and B/Florida/4/2006-like antigens.¹ Live, attenuated-virus vaccine is currently approved only for healthy, nonpregnant persons aged 5—49 years.

Table 1. Influenza Vaccination Recommendations, 2008:Children and Adolescents Aged Six months to 18 years*+

• Vaccination of all children aged six months —18 years should begin before or during the 2008–2009 influenza season if feasible, but no later than during the 2009–2010 influenza season. Vaccination of all children aged 5-18 years in a new ACIP recommendation.

• Children and adolescents at high risk for influenza complications should continue to be a focus of vaccination efforts as providers and programs transition to routinely vaccinating all children and adolescents. Recommendations for these children have not changed.

• Children and adolescents at higher risk for influenza complications are those: — Aged six months–4 years – Who have chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological or metabolic disorders (including diabetes) – Who are immunosuppressed (including immunosuppression caused by medications or by human immunodeficiency virus) – Who have any condition (eg, cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders) that can compromise respiratory function or the handling of respiratory secretions or that can increase the risk for aspiration – Who are receiving long-term aspirin therapy who therefore might be at risk for experiencing Reye syndrome after influenza virus infection – Who are residents of chronic-care facilities – Who will be pregnant during the influenza season.

ACIP = Advisory Committee on Immunization Practices.

*Recommendations of the ACIP, 20081,7

†Children aged <6 months should not receive influenza vaccination. Household and other close contacts (eg, daycare providers) of children aged <6 months, including older children and adolescents, should be vaccinated.

Table 2. Influenza Vaccination Recommendations, 2008:Adults*

• Annual recommendations for adults have not changed. Annual vaccination against influenza is recommended for any adult who wants to reduce the risk for becoming ill with influenza or of transmitting it to others.

• Vaccination also is recommended for all adults in the following groups, because these persons are either at high risk for influenza complications, or are close contacts of persons at higher risk:

— Persons aged ≥ 50 years

— Women who will be pregnant during the influenza season

— Persons who have chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, hematological, or metabolic disorders (including or metabolic disorders (including diabetes)

— Persons who immunosuppression (including immunosuppression caused by medications or by human immunodeficiency virus)

— Persons who have any condition (e.g., cognitive dysfunction, spinal cord injuries, seizure disorders, or other neuromuscular disorders) that can compromise respiratory function or the handling of respiratory secretions or that can increase the risk for aspiration

— Residents of nursing homes and other chronic-care facilities

— Health care personnel

— Household contacts and caregivers of children aged <5 years and adults aged ≥50 years, with particular emphasis on vaccinating contacts of children aged <6 months

— Household contacts and caregivers of persons with medical conditions that put them at high risk for severe complications from influenza.

*Recommendations of the Advisory Committee on Immunization Practices, 2008

¹

Flu Vaccination in Patients With Cancer

According to the CDC, less than 30% of patients with high-risk conditions, including cancer, were vaccinated against flu in 2005.⁸ Table 3 shows flu vaccination coverage levels in persons with high-risk conditions, including cancer, by age. Data shown in the table were derived from the National Health Interview Survey and National Immunization Survey, US, 2005.

The results of a survey presented on October 27, 2007 at the 49th annual meeting of the American Society for Therapeutic Radiation and Oncology (ASTRO) in Los Angeles (Poster 2641) highlight the poor flu vaccination coverage in patients with cancer specifically.⁹ About a third of patients who responded to an anonymous survey said they had not had a flu vaccination, according to Neha Vapiwala, MD, University of Pennsylvania, Philadelphia, PA, and one of the authors of the presented study.

The survey was completed by 214 consecutive cancer outpatients at the University of Pennsylvania from August 2006 to January 2007. Ninety-eight percent of the questionnaires were complete and usable for analysis. This was the first performed to evaluate whether patients with cancer are compliant with national vaccination guidelines. Patients who reported not receiving flu vaccine were asked further questions about the reasons why they didn’t receive it.

Key findings from the study were as follows⁹:

• Thirty percent of patients said they had never had the flu vaccine, and another 9% said they were not getting vaccinated yearly.

• About 60% of unvaccinated patients said they didn’t know they needed a flu shot.

• Among patients aged 50 and older—i.e., those recommended for a flu shot&mdash;33% had never been vaccinated.

• Among patients who got their shots, 66% said they heard about the vaccines from a health care provider other than one providing cancer care. Only ten% of patients were told about flu vaccine by an oncologist.

Dr. Vapiwala reiterated, “Despite being seen by many clinicians for their cancer care, only one in ten patients who actually got vaccinations said the shots had been recommended by their oncologist.”

When asked about potential reasons for the suboptimal flu vaccination in patients with cancer, Dr. Vapiwala explained, “It’s a communications gap. Oncologists tend to assume that vaccinations are being handled by the primary care provider, while the primary care physician may assume the opposite. It’s not clear to patients and it’s not clear to physicians necessarily who is responsible for what.”

Clearly, a key reason for not receiving flu vaccine was not knowing about the vaccine, thinking it was not needed, or not having it recommended by a physician. The issue is important because patients who have malignancies and who undergo cancer treatment are at greater risk of acquiring viral illnesses such as influenza. They also tend to have a more severe course and a more difficult recovery once they develop an infection.

Although the study was small and focuses on a single institution, Dr. Vapiwala said she thinks the communication gap is a general problem. “Somebody has to take responsibility [for routine care issues], and right now, it’s a gray area.” She added, “Oncologists have the opportunity to talk to patients about recommended vaccines during their frequent interactions with patients, whether it be before, during, or after cancer therapy. This discussion could result in better cancer care and ultimately save lives.”

Table 3. Influenza Vaccination Coverage Levels in Persons with High-Risk Conditions, Including Cancer*⁸

Age - Group

Crude Sample Size

Vaccination Level % (95 CI)

2 - 17 years

985

28.4 (25.3 - 31.8)

18 - 49 years

2576

18.0 (16.3 - 19.7)

50 - 64 years

2350

34.2 (32.0 - 36.4)

18 - 64 years

4926

25.3 (24.0 - 26.7)

* “Cancer” refers to having a diagnosis of cancer during the previous 12 months (excluding nonmelanoma skin cancer) or being told by a physician of a diagnosis of lymphoma, leukemia, or blood cancer during the previous 12 months.

CI = confidence interval

Newest Trivalent Influenza Vaccine

Afluria is a mercury-free, purified, inactivated, trivalent influenza vaccine propagated in embryonic chicken eggs. Each dose contains the required dose of influenza virus hemagglutinin antigens from the influenza strains recommended and prioritized by the FDA’s Vaccine and Related Biological Products Advisory Committee for each flu season. Afluria was approved by the FDA in September 2007 for the active immunization of persons ≥18 years of age against influenza disease caused by influenza subtypes A and type B present in the vaccine.

Conclusion

The CDC recommend an annual flu shot for patients with cancer 50 years and older and yearly pneumonia shots for patients older than 65 years. In a 2007 survey of people undergoing radiation treatment for cancer, scientists found that among those who meet CDC guidelines for annual vaccination, 25% have never had a flu shot and more than 30% had never been vaccinated against pneumonia.

Since patients with cancer have weakened immune systems, they are especially susceptible to flu and pneumonia. Family members and close contacts of these individuals also have an increased risk of infection and the CDC advises them to make annual vaccinations a health priority.

References1. Centers for Disease Control and Prevention. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2008. MMWR 2008;57:1-60.2. Centers for Disease Control and Prevention. Update: Influenza activity—United States and worldwide, 2006—2007 season, and composition of the 2007–2008 influenza vaccine. MMWR 2007;56:789-794.3. Thompson WW, Shay DK, Weintraub E, et al: Mortality associated with influenza and respiratory synctyial virus in the United States. JAMA 2003;289:179-186.4. Thompson WW, Shay DK, Weintraub E, et al: Influenzaassociated hospitalizations in the United States. JAMA 2004;292:1333-1340.5. Barker WH, Mullooly JP: Impact of epidemic type A influenza in a defined adult population. Am J Epidemiol 1980;112:798-811.6. Neuzil KM, Wright PF, Mitchel EF, et al: The burden of influenza illness in children with asthma and other chronic medical conditions. J Pediatr 2000;137:856-864.7. Centers for Disease Control and Prevention. Influenza vaccine workgroup report. 2008. Available at: http:// www.cdc.gov/vaccines/recs/acip/downloads/mtgslides- jun08/32-3-flu.pdf. Accessed August 9, 2008.8. Centers for Disease Control and Prevention. Prevention and control of influenza. Recommendations of the Advisory Committee on Immunization Practices (ACIP), 2007. MMWR 2007;56:1-54.9. Yee S, Dutta P, Solin L, et al: Compliance with national vaccination guidelines in patients receiving radiation therapy. Int J Rad Onc Biol Physics 2007;69(suppl):S560.