Risk Factors for Persistent Hypogammaglobulinemia in Pediatric and Young Adult Patients Receiving Rituximab

Rationale Rituximab is an anti-CD20 monoclonal antibody that can cause persistent hypogammaglobulinemia (PH) in 20–45% of patients, depending on the patient population. Risk factors for PH in pediatric patients following rituximab have been inconsistently identified. Prediction and timely identification of patients at risk for PH can enable earlier treatment with immunoglobulin replacement, preventing infectious complications. Methods We conducted a retrospective analysis of all patients who received rituximab (2017–2021) at an academic pediatric tertiary care center who had post-rituximab immunoglobulin G (IgG) assessed. Patients were excluded if they received rituximab for oncologic indications, underwent hematopoietic stem cell transplantation, received scheduled immunoglobulin replacement pre-rituximab, or had known humoral immunodeficiency. PH was defined as low IgG <2 standard deviations for age beyond one year from the most recent rituximab dose or, in the absence of a 1-year post-rituximab IgG level, new, continuous immunoglobulin replacement. We evaluated demographic, clinical, and laboratory characteristics that could predict PH using univariate and multivariate logistic regression. Post-rituximab absolute CD19 counts obtained greater than 1 year after the most recent rituximab dose were analyzed. Results A total of 206 patients met criteria, with the majority receiving rituximab for rheumatologic (34%), neurologic (33%), renal (14%), or hematologic (8%) indications. Median age at first dose of rituximab was 14.1 years (interquartile range [IQR] 8.7, 16.8), 59% were female, and 57% identified race as non-White. PH was observed in 42 (20.3%) patients. In univariate analysis, lower age (odds ratio [OR] 0.92, 95% confidence interval [CI]: 0.86, 0.97), Black race (OR 0.37, CI 0.13, 0.92), pre-rituximab IgM (OR 3.7, CI 1.2, 10.8), and post-rituximab absolute CD19 (OR 5.6, CI 2.5, 12.6) and IgA (OR 5.5, CI 2.4, 12.8) were associated with PH. Post-rituximab IgA was obtained at a median of 0.7 years (IQR 0.3, 2.2), and the first low absolute CD19 was obtained at median 1.3 years (IQR 1.1, 2.1) after the most recent rituximab dose. On multivariate analysis adjusting for age, post-rituximab low absolute CD19 (OR 6.5, CI 2.4, 19.3) and low IgA (OR 6.0, CI 2.5, 16.0) were associated with PH. Conclusion In a large, diverse cohort of pediatric and young adult patients, low post-rituximab absolute CD19 and IgA were risk factors for the development of persistent hypogammaglobulinemia. Tabular data are included as downloadable supplement files.