Illustrative Case Series

Vaccination Considerations for Chemotherapy Patients

By William B. Ershler, MD

A 58-year-old female patient with non-Hodgkin lymphoma is seen in the medical oncology clinic for the initiation of the fourth cycle of chemotherapy (R-CHOP). She had presented approximately 3 months earlier with asymptomatic lymphadenopathy. Computerized tomography revealed enlarged lymph nodes throughout the chest and abdomen and an axillary node biopsy revealed follicular large B-cell lymphoma. A bone marrow biopsy was negative for lymphoma involvement. The first three cycles of chemotherapy were tolerated very well with resolution of all palpable disease. On the occasion of initiation of her fourth cycle, she inquired about the advisability of receiving both influenza and shingles vaccines.

The patient’s past medical history was significant for insulin-requiring diabetes mellitus and hypertension for which she received metoprolol 12.5 mg bid. She had remained without constitutional complaints throughout therapy and continues to work full time as a waitress.

Discussion

Patients with cancer in general, but particularly those with hematologic malignancies, are at increased risk for infectious diseases, some of which are preventable by vaccination.1,2 Risk for infection is heightened by the immunosuppressive effects of chemotherapy, with some agents, such as rituximab being particularly powerful at diminishing vaccine response.3

Although immunization appears to be an obvious way to prevent infection, many patients with impaired immunity are unable to mount a protective immune response to active vaccination. Furthermore, studies demonstrating efficacy of vaccines in patients with cancer are insufficient to provide formal evidence-based guidelines for the prevention of vaccine-preventable infections in oncology patients (excluding those who undergo hematopoietic cell transplantation). Nonetheless, immunization recommendations for immunocompromised patients in the United States have been developed by the Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC). In general, immunocompromised patients, such as those with cancer, should receive only inactivated vaccines (such as influenza and pneumococcal vaccines) and not live virus vaccines, such as the zoster vaccine.4

Influenza vaccine. Influenza-related hospitalization is 3-5 times higher in cancer patients than the general population and the mortality rate is 9% (relative risk 4, compared with the general population).5 Accordingly, annual vaccination is strongly recommended for those with cancer.6 Furthermore, antiviral prophylaxis should be considered for those undergoing the most intense chemotherapy under certain circumstances, such as following an exposure. As mentioned, certain systemic anticancer agents have profound effects on immunity. A recent study aimed to determine whether lymphoma patients receiving rituximab-containing treatment regimens during or within the prior 6 months were able to mount protective antibody responses to the influenza A (H1N1) 2009 virus. The investigators found that contrary to age-matched controls without lymphoma in whom 82% responded adequately to the vaccine, none of the 67 patients achieved protective antibody titers.3 In earlier studies, the same group reported adequate influenza vaccine responses among non-Hodgkin lymphoma patients receiving combination chemotherapy without rituximab.7,8 Thus, rituximab appears particularly suppressive with regard to vaccine response — an observation that warrants recognition by clinicians in formulating vaccine schedules and considering use of antivirals.

It makes sense that the optimal time to receive a vaccine is before the initiation of chemotherapy. However, due to the seasonal nature of influenza vaccination programs, such timing often is not feasible. The optimal time for vaccination in patients already receiving chemotherapy is not established. In a recent report of breast cancer patients receiving FEC (5-fluorouracil, epirubicin, and cyclophosphamide)-containing chemotherapy regimens, patients were randomized to receive influenza vaccine early in the cycle (day 4) or at mid-cycle (day 16). As expected, the overall patient group had significantly lower responses to the vaccine compared with healthy controls. However, patients vaccinated at day 4 tended to have higher antibody titers compared to patients vaccinated at day 16. Thus, at least for breast cancer patients on combination chemotherapy, vaccination early during the chemotherapy cycle induces better responses than does vaccination at day 16. Whether this finding can be generalized to patients receiving other chemotherapies for other tumors remains to be studied.

Pneumococcal vaccine. Infections due to Streptococcus pneumoniae are an important cause of morbidity and mortality in oncology patients. Cancer patients are known to respond variably to the 23-valent pneumococcal polysaccharide vaccine, although responses are almost comparable to age-matched controls if the vaccine is given prior to chemotherapy.9 However, responses after chemotherapy, even years later, have been shown to be suboptimal.10

Although a novel protein conjugated pneumococcal vaccine (Prevnar-13) currently has been approved for use in the United States, its efficacy in patients who are immunocompromised has yet to be established. It is expected that vaccine schedules including both the conjugate and polysaccharide vaccines will be developed for immunocompromised patients, but these have yet to be provided.

Zoster vaccine. Although patients with malignancy are at increased risk for shingles, the zoster vaccine (Zostavax) is a live-attenuated virus and its use is contraindicated in cancer patients. Nonetheless, the CDC suggests that patients with hematological cancers in remission and off chemotherapy (and radiotherapy) for 3 or more months may receive zoster vaccine.4

Recommendation

For the patient presented, both influenza and pneumococcal vaccines would be recommended. Timing of the vaccines might prove critical, and based on the limited data available, the influenza vaccine might best be given shortly after the initiation of the next cycle of chemotherapy. However, because of the inclusion of rituximab in the treatment program, a suboptimal response might be expected. Thus, the patient should be informed that infection with influenza remains a concern despite the vaccine and that she would be a candidate for antiviral medications shortly after symptoms of influenza are noticed. Similarly, the published experience suggests a suboptimal response to the polysaccharide pneumococcal vaccine would be expected. In this regard, new recommendations about the use of the pneumococcal conjugated vaccine either alone or in sequence with the polysaccharide vaccine will be of great value.

References

1. Brown AE. Influenza and pneumococcal immunization of patients with neoplastic diseases. Schweiz Med Wochenschr Suppl 1983;14:30-34.

2. Gross PA, et al. Effect of cancer chemotherapy on the immune response to influenza virus vaccine: Review of published studies. Rev Infect Dis 1985;7:613-618.

3. Yri OE, et al. Rituximab blocks protective serologic response to influenza A (H1N1) 2009 vaccination in lymphoma patients during or within 6 months after treatment. Blood 2011;118:6769-6771.

4. National Center for Immunization and Respiratory Diseases. General recommendations on immunization. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep 2011;60:1-64.

5. Boehmer LM, et al. Influenza vaccination in patients with cancer: An overview. Oncology 2010;24:1167-1170.

6. Centers for Disease Control and Prevention (CDC). Prevention and control of influenza with vaccines: Recommendations of the Advisory Committee on Immunization Practices (ACIP). United States, 2012-2013 influenza season. MMWR 2012;61.

7. Brydak LB, et al. Humoral response to hemagglutinin components of influenza vaccine in patients with non-Hodgkin malignant lymphoma. Vaccine 2006;24:6620-6623.

8. Centkowski P, et al. Immunogenicity of influenza vaccination in patients with non-Hodgkin lymphoma. J Clin Immunol 2007;27:339-346.

9. Siber GR, et al. Antibody response to pretreatment immunization and post-treatment boosting with bacterial polysaccharide vaccines in patients with Hodgkin’s disease. Ann Intern Med 1986;104:467-475.

10. Frederiksen B, et al. Antibody response to pneumococcal vaccine in patients with early stage Hodgkin’s disease. Eur J Haematol 1989;43:45-49.