Pre-Rituximab Immunoglobulin Testing and Baseline Hypogammaglobulinemia Across Rituximab Indications in Adults: A Multisite Retrospective Study.

Abstract

Baseline immunoglobulin assessment before initiating B-cell-targeted therapies identifies pre-existing hypogammaglobulinemia (HG) and facilitates interpretation of post-treatment immune dysfunction. Historically, pre-treatment IgG testing rates have been low (<15%), and contemporary practice patterns remain poorly characterized. To characterize pre-rituximab serum total IgG testing, baseline HG, and pre-treatment immunoglobulin replacement therapy (IgRT) use across rituximab indications. We performed a multisite retrospective study of 1184 patients receiving their first rituximab infusion at Mayo Clinic between November 1, 2024, and November 1, 2025. We assessed IgG testing within 1 year and 60 days before rituximab, baseline IgG levels (HG defined as IgG <700 mg/dL), and pre-treatment IgRT use. Multivariable models evaluated factors associated with IgG testing and levels. In a predominantly adult (1159/1184 [98%]) cohort, IgG was measured within 1 year before rituximab in 663/1184 patients (56%) and within 60 days in 514/1184 (43%). Testing rates varied by disease specialty, from 5/37 (14%) in dermatology to 60/74 (81%) in neurology (overall P<.001). Among patients tested within 60 days, 144/514 (28%) had HG and 35/514 (7%) had IgG <400 mg/dL. HG prevalence varied by disease category, including 16/20 (80%) in nephrotic syndrome and 24/40 (60%) in chronic/indolent leukemia. Among patients with baseline HG, 15/144 (10%) received pre-treatment IgRT: 11 replacement-dose IVIG, 4 immunomodulatory-dose IVIG, and 0 subcutaneous immunoglobulin. In contemporary rituximab practice, baseline IgG testing has increased but remains incomplete, and HG is common among those tested. Specialty- and disease-specific variation identifies opportunities to standardize pre-treatment immunoglobulin assessment. Optimal management of baseline HG remains undefined.