Serum antibody response to influenza virus vaccination during chemotherapy treatment in adult patients with solid tumours

Highlights

• We studied the serum antibody response in patients receiving chemotherapy.

• Overall antibody response to the influenza virus vaccine is adequate.

• Breast cancer patients mount the best serum antibody response early after receiving chemotherapy (≤day 5).

Abstract

Background

Higher rates of hospitalization and mortality are described in oncology patients with influenza virus infection compared to the general population. Yearly influenza vaccination is recommended for patients treated with chemotherapy. The optimal moment to administer the vaccine during a treatment cycle has not been studied extensively.

Patients and methods

During the influenza season 2011–2012 we conducted a multicenter randomized controlled trial (OFLUVAC, NTR2858, no sponsoring) in the Netherlands. Patients receiving adjuvant chemotherapy for breast or colorectal cancer were randomized between early (day 5 after chemotherapy) and late (day 16 after chemotherapy) vaccination with the influenza virus vaccine (Influvac^® 2011/2012—Vaxigrip^® 2011/2012). Influenza virus-specific antibody titres were determined before, 3 and 12 weeks after vaccination by haemagglutination inhibition.

Results

Thirty-eight breast cancer patients (early = 21; late = 17) and 18 colorectal cancer patients (early = 8; late = 10) were analyzed. In breast cancer patients overall serologic responses were adequate. A statistically significant higher response in patients who received early compared to late vaccination in the chemotherapy cycle was observed. Geometric mean titres post vaccination on day 5 versus day 16 were 69.3 versus 27.4 (H3N2), 76.4 versus 17.5 (H1N1) and 34.4 versus 26.0 (B/Brisbane), respectively.

In colorectal cancer patients overall serologic responses were adequate, no significant difference was found between early and late vaccination. Geometric mean titres post vaccination on day 5 versus day 16 were 170.1 versus 192.4 (H3N2), 233.0 versus 280.8 (H1N1) and 62.6 versus 75.9 (B/Brisbane), respectively.

Conclusion

Overall antibody response to the influenza virus vaccine in patients treated with chemotherapy for breast or colorectal cancer patients is adequate. Breast cancer patients seem to mount the best antibody response when vaccinated early after a chemotherapy cycle (≤day 5). No difference was found between early and late vaccination in colorectal cancer patients.

Introduction

Higher rates of hospitalization and mortality are described in oncology patients with influenza virus infection compared to the general population [1]. Because of immunosuppressive factors influencing the response to viral infections, patients with cancer are at risk for serious post-influenza complications including secondary bacterial pneumonia, otitis media, sinusitis or deterioration of chronic respiratory or cardiac conditions [2]. Therefore, yearly influenza vaccination is strongly recommended for patients treated with chemotherapy or other immunosuppressive drugs [3], although their immune response may be suboptimal [4]. Two factors influence the immune status and the response to immunization in patients with cancer. First, their disease state can be directly immunosuppressive, this is of particular importance in haematological malignancies. Second, most treatment modalities for cancer have (severe) immunosuppressive effects. Chemotherapy is designed to destroy rapidly growing tumour cells, but will inevitably also impair haematopoiesis. Moreover, full functional capacity of cells of the immune system depends on clonal expansion of antigen specific lymphocytes and is therefore adversely affected [5].

Despite the recommendations and availability of effective influenza vaccines, vaccination coverage is low in cancer patients with chemotherapy treatment [6]. This may be due to conflicting conclusions on the efficacy and optimal moment of administering the vaccine as well as the lack of (inter)national guidelines. Indeed, limited data are available on the utility of influenza vaccination during ongoing chemotherapy regimens. Several studies of patients with lung and breast cancer, with or without receiving treatment, showed these patients have the ability to mount protective antibody titres to influenza vaccination ([5], [7], [8], [9] reviewed by [10]).

In general, it is recommended to vaccinate before start of chemotherapy treatment [10], [11]. However, many patients are vaccinated while on chemotherapy because the seasonal influenza vaccination campaign is restricted to the months October and November and because of the duration of the treatment course.

The optimal moment to administer the vaccine during a treatment cycle remains unclear [8]. Current recommendations, to vaccinate on the furthest time point from chemotherapy, are based on a single study from 1977 which included only a very limited number of patients (n = 11) [12].

During the influenza vaccination period in 2009, we have conducted a pilot study in patients with breast cancer. Breast cancer patients receiving chemotherapy, were randomized for early (day 4 of the chemotherapy cycle) or late (day 16 of the chemotherapy cycle) influenza vaccination. In this study, patients vaccinated at day 4 tended to reach higher antibody levels compared to patients vaccinated at day 16 [9].

To confirm this observed effect we designed a study in which we evaluate the antibody response to influenza vaccination during chemotherapy and assess the effect of timing of influenza vaccination during chemotherapy in breast cancer and colorectal cancer patients.