Rituximab-induced Hypogammaglobulinemia and Infection Risk in Pediatric Patients

J Allergy Clin Immunol. 2021 Apr 13;S0091-6749(21)00564-9. doi: 10.1016/j.jaci.2021.03.041. Online ahead of print.

Abstract

Background: Rituximab (RTX) is a B-cell depleting agent used in B-cell malignancies and autoimmune diseases. A subset of adult patients may develop prolonged and symptomatic hypogammaglobulinemia following RTX. However, this phenomenon has not been well delineated in the pediatric population.

Objective: To determine the prevalence, risk factors and clinical significance of hypogammaglobulinemia following RTX therapy in children.

Methods: We conducted a multi-center, retrospective cohort study and extracted clinical and immunological data from pediatric patients who received RTX.

Results: The cohort was comprised of 207 patients (median age 12.0 years). Compared to baseline values, there was a significant increase in hypogammaglobulinemia post-RTX, with an increase in prevalence of hypo-IgG (28.7% to 42.6%, p=0.009), hypo-IgA (11.1% to 20.4%, p=0.02) and hypo-IgM (20.0% to 62.0%, p<0.0001). Additionally, low IgG levels at any time post-RTX were associated with a higher risk of serious infections (34.4% vs 18.9%; OR 2.3, 95% CI 1.1-4.8, p=0.03). Persistent IgG hypogammaglobulinemia (PH-IgG) was observed in 27 (26.7%) of 101 evaluable patients. Significant risk factors for PH-IgG included low IgG and IgA levels pre-RTX. Nine patients (4.3%) within the study were subsequently diagnosed with a primary immunodeficiency (PID), seven of which received RTX for autoimmune cytopenias.

Conclusion: Hypogammaglobulinemia post-RTX is frequently diagnosed within the pediatric population. Low IgG levels are associated with a significant increase in serious infections, and underlying PIDs are relatively common in children receiving RTX, thus highlighting the importance of immunologic monitoring both before and after RTX therapy.

Keywords: B-cell depleting therapy; IgG; children; hypogammaglobulinemia; immunoglobulin; infection; pediatrics; primary immunodeficiency; rituximab; secondary immunodeficiency.