Impaired Response to Influenza Vaccine Associated with Persistent Memory B Cell Depletion in Non-Hodgkin’s Lymphoma Patients Treated with Rituximab-Containing Regimens

Abstract

Influenza vaccination is generally recommended for non-Hodgkin’s lymphoma (NHL) patients, but no data are available about the activity of this vaccine after treatment with rituximab-containing regimens. We evaluated the humoral response to the trivalent seasonal influenza vaccine in a group of NHL patients in complete remission for ≥6 mo (median, 29 mo) after treatment with rituximab-containing regimens (n = 31) compared with age-matched healthy subjects (n = 34). B cell populations and incidence of influenza-like illness were also evaluated. For each viral strain, the response was significantly lower in patients compared with controls and was particularly poor in patients treated with fludarabine-based regimens. In the patient group, the response to vaccination did not fulfill the immunogenic criteria based on the European Committee for Medicinal Products for Human Use requirements. Among the patients, CD27+ memory B cells were significantly reduced, and their reduction correlated with serum IgM levels and vaccine response. Episodes of influenza-like illness were recorded only in patients. These results showed that NHL patients treated with rituximab-containing regimens have persisting perturbations of B cell compartments and Ig synthesis and may be at particular risk for infection, even in long-standing complete remission.

Rituximab blocks protective serologic response to influenza A (H1N1) 2009 vaccination in lymphoma patients during or within 6 months after treatment

“…16 Some studies with limited patient numbers have suggested that rituximab has a negative impact on response to influenza vaccine, both during treatment 12,13 and more than 6 months after treatment. 14 Takata et 12 and van der Kolk et al reported a reduced immune response after rituximab therapy in 11 patients. 13 Bedognetti et al found significantly lower responses to the 2008-2009 seasonal vaccine in 31 non-Hodgkin lymphoma patients treated with rituximab-containing regimens.…”

“…14 Unlike our study, these 31 patients had completed treatment 6 months or more before vaccination. 14 The present study represents the first large controlled study aimed to investigate humoral responses to influenza vaccination in lymphoma patients treated with rituximab as a single agent or in combination with chemotherapy. No vaccine-induced protective immunity was observed in any cases against the influenza A (H1N1) 2009 ("swine flu") virus.…”

“…[7][8][9][10] Rituximab may dramatically impair the humoral response to vaccination in rheumatoid arthritis patients, 11 but only a few studies have addressed this effect in rituximab-treated lymphoma patients. [12][13][14] We have conducted a controlled study where serologic response to the influenza A (H1N1) virus vaccine Pandemrix during the 2009 "swine flu" pandemic was analyzed in 67 lymphoma patients treated with rituximab monotherapy or in combination with chemotherapy within the last 6 months before vaccination and compared it with the response in 51 healthy controls.…”

Robust memory responses against influenza vaccination in pemphigus patients previously treated with rituximab

“…To our knowledge, there are no reports describing vaccine efficacy in rituximab-treated AIBD patients. Previous studies have reported severely impaired immune responses to influenza vaccination in other types of rituximab-treated patients, primarily RA or lymphoma patients (30)(31)(32)(33)(34). A major caveat to these earlier studies is that patients were treated with concomitant immunosuppressive drugs or chemotherapy, making it difficult to determine the effect of the individual drugs on vaccine responses.…”

BI 1002494, a Novel Potent and Selective Oral Spleen Tyrosine Kinase Inhibitor, Displays Differential Potency in Human Basophils and B Cells

“…However, there is no direct evidence that B-cell depletion and/ or loss of function would be beneficial in asthma, and loss of regulatory B cells exacerbates allergic airway inflammation in mice (Amu et al, 2010). Furthermore, compromising B-cell function may even be deleterious in patients with asthma who rely on vaccine protection from respiratory viruses (e.g., influenza) to prevent exacerbation (Wells et al, 2015), and there is evidence that B-cell depletion impairs response to the influenza vaccine (Bedognetti et al, 2011). However, fostamatinib demonstrated no effect on IgG or IgM responses after keyhole limpet hemocyanin challenge, nor did it affect bacterial or viral clearance in listeria, streptococcal, or influenza host-resistance mouse models (Zhu et al, 2007), suggesting that B-cell responses may not be impaired, even at higher exposures that cover the CD69 activation assay.…”