Immunodeficiency: primary or acquired
Introduction: Rituximab is a chimeric monoclonal antibody for treating hematologic and autoimmune diseases by depleting CD20-expressing B-cells. Hypogammaglobulinemia following rituximab treatment has been reported. Risk stratification for developing severe infection would identify patients who may benefit from immunoglobulin replacement therapy. The aim of this systematic review was to describe the prevalence of hypogammaglobulinemia and its risk for developing severe infection.
Method: We performed an electronic search of Ovid Medline, Embase, Web of Science, Scopus and the Cochrane Library identifying studies describing the prevalence of hypogammaglobulinemia following initiation of rituximab.
Results: 16 studies met eligibility criteria. Study sample size was between 12 and 3595 patients (median 177). Cohort studies included lymphoma patients receiving maintenance rituximab, with combination chemotherapy or in association with autologous bone marrow transplant (6 studies). 8 cohort studies described prevalence of rituximab-induced hypogammaglobulinemia following treatment for multisystem autoimmune disease including rheumatoid arthritis (3), systemic lupus erythematosus (2), systemic autoimmune disorders (2) and granulomatosis with polyangiitis (1). Hypogammaglobulinemia prevalence was between 3.5 and 45%; lowest prevalence in on maintenance rituximab in follicular lymphoma (0.9%) and highest in granulomatosis with polyangiitis (45%). Prevalence of severe infection ranged from 3.9 to 46%. Risk factors for infection included low baseline immunoglobulin, female gender and treatment with cyclophosphamide, fludarabine or glucocorticoids.
Conclusions: Prevalence of hypogammaglobulinemia is widely variable owing to the heterogeneity of patient cohorts with multifactorial disease and treatment-related etiologies for hypogammaglobulinemia. Monitoring baseline serum immunoglobulin and B-cell levels is essential to identify patients at risk of developing severe and recurrent infection.