Evaluation of pandemic H1N1 (2009) influenza vaccine in adults with solid tumor and hematological malignancies on active systemic treatment
Introduction
Patients undergoing chemotherapy are reported to be at increased risk of contracting, suffering complications and dying from seasonal influenza.1, 2, 3 The Centers for Disease Control and Prevention (CDC) recommends annual vaccination for patients on chemotherapy.4 However, limited and conflicting data exists to inform the clinician on the efficacy of vaccination programs in this patient population.5, 6, 7, 8, 9, 10 As a result, despite recommendations, less than half of patients on chemotherapy undergo vaccination.11, 12 Dialogue between patients and oncologists is variable, one study suggesting it may occur in as few as 7% of cases.13
In March of 2009, an influenza A H1N1 virus – H1N1 (2009) – was linked to an outbreak of respiratory infections in Mexico, launching a worldwide pandemic.14, 15 A subunit inactivated monovalent vaccine – the H1N1 (2009) pandemic vaccine – was generated from the influenza A/California/7/2009 viral strain and made available through public vaccination programs. Vaccination dosing and schedule for the pandemic vaccine were developed using healthy individuals.16, 17
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Objectives
To evaluate rates of seroprotection and seroconversion following H1N1 (2009) vaccination in two patient populations receiving cytotoxic chemotherapy: patients with solid tumors; and those with hematological malignancies. Secondary aims included providing safety data on the vaccine and exploring physicians’ attitudes to vaccination.
Design
Patients actively receiving cytotoxic chemotherapy for solid tumor and hematological malignancy in ambulatory clinics at the Princess Margaret Hospital, Toronto, Canada were approached to participate in this study assessing serological response to ASO 3-adjuvanated H1N1 pandemic influenza vaccine Arepanrix™ (GlaxoSmithKline). The study was approved by the Local Research Ethics Board. All patients signed written informed consent prior to study entry. A separate survey of clinician attitudes to
Results
A total of 46 patients, median age was 56 years, had paired sera available for analysis. 50% of patients had undergone seasonal flu vaccination in previous seasons (no patient had undergone 2009 seasonal flu vaccination); additional characteristics are shown in Table 1. Amongst the solid tumor patients 12 were receiving a platinum based combination chemotherapy and seven single agent treatment. The most common co morbidities were hypertensions, hyperlipidaemia and type 2 diabetes. Concurrent
Discussion
Studies measuring immunogenicity following vaccination with a single dose of pH1N1 vaccine in the general population have shown seroprotection rates over 85%.16, 17, 21 To the best of our knowledge, this represents the first report on the effect of pH1N1 vaccination in patients undergoing chemotherapy. Although well tolerated, we observed lower rates of seroprotection (37%) and serconversion (30%) than would be expected in the general population. Rates were lowest in patients with hematological
Funding
Medical Gynecology Research Fund, PMH Foundation.
Conflict of interest
No conflict of interest to declare.
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Cited by (29)
Vaccination of patients with haematological malignancies who did not have transplantations: guidelines from the 2017 European Conference on Infections in Leukaemia (ECIL 7)
2019, The Lancet Infectious DiseasesCitation Excerpt :Rituximab is widely used in both B-cell lymphoma and CLL. However, it strongly impairs—often annihilates—the response to IIV,38,70,71,93 even in case of two doses71 or ASO3-adjuvanted vaccine.38,67,70,71 When patients were vaccinated at 6–10 months38,67 or even within a median of 29 months66 after the last rituximab dose, the response was 0–29%.
Safety and immunogenicity of inactivated varicella-zoster virus vaccine in adults with hematologic malignancies receiving treatment with anti-CD20 monoclonal antibodies
2017, VaccineCitation Excerpt :However, hematopoietic progenitor cells and most differentiated plasma cells do not express CD20, which limits the immunosuppressive effect of rituximab. The effect of rituximab on the response to antigen by humoral or cellular pathways is unclear, with conflicting data from different vaccine studies [16–19]. The purpose of this Phase I study (NCT01460719) was to evaluate the safety and immunogenicity of 4 doses of ZVIN in HM patients receiving anti-CD20 monoclonal antibodies, either as a single agent or in combination with chemotherapy.
The effect of rituximab on vaccine responses in patients with immune thrombocytopenia
2013, BloodCitation Excerpt :In patients with lymphoma previously treated with high-dose chemotherapy, rituximab was associated with an inadequate antibody response to pneumococcal vaccine but a preserved response to tetanus toxoid and Hib vaccines.44 The addition of rituximab to chemotherapy in 11 patients with hematological malignancies resulted in a failure to respond to the H1N1 vaccine,14 and low rates of seroconversion were observed in 14 patients with lymphoid malignancies; however, responses were not significantly different from control patients who did not receive rituximab.45 In one study of patients with rheumatoid arthritis (n = 14), rituximab was not associated with an impaired antibody response to 2 of 3 influenza virus antigens even during profound B-cell depletion15; whereas in another study (n = 17) a poor response to the influenza vaccine was observed.10
Pandemic whole-virion, Vero-cell-derived, adjuvant-free influenza A H1N1 vaccine in patients with solid tumors and hematologic malignancies receiving concurrent anticancer treatment: Immunogenicity, tolerability, and acceptability during the pandemic situation
2012, VaccineCitation Excerpt :Even in patients with hematologic malignancies, a seroconversion rate of 75% (similar to that in healthy controls) was observed. In contrast to the literature [44,45], the authors concluded that myelosuppressive and/or immunosuppressive chemotherapy in general does not hamper the ability of cancer patients to generate an anti-H1N1 immune response. Their results may be due to the type of vaccine, the heterogenous mix of patients with hematologic malignancies, and differing treatment regimes.