Effect of immunoglobulin-replacement therapy on the incidence of severe infections in patients with chronic lymphocytic leukemia

Abstract Introduction: Patients with chronic lymphocytic leukemia (CLL) are at increased risk of secondary hypogammaglobulinemia (HGG), which may be triggered by CLL itself and/or its treatments. HGG is associated with a higher risk of severe infections, which are one of the major causes of morbidity and mortality in patients with CLL (Allegra et. al. Front Immunol 2021). Clinical guidelines recommend screening for HGG and initiating immunoglobulin replacement therapy (IgRT) in patients with CLL, HGG and severe, recurrent, or unusual infections (Otani et. al. J Allergy Clin Immunol 2022). This study aims to assess the effectiveness of Immunoglobulin Injection (Human),10%, Caprylate/Chromatography Purified (IGIV-C10%) on the risk of severe infections in patients with CLL presenting with HGG using recent real-world US data. Methods: A retrospective cohort study was conducted using US insurance claims data from the PharMetrics Plus database. Patients diagnosed with CLL (≥2 claims with an ICD-10-CM code for CLL at least 30 days apart), who developed HGG (presence of an inpatient or outpatient claim with one the following ICD-10-CM codes: D80.1, D80.3, D80.9) on or after CLL diagnosis, and received ≥4 doses of IGIV-C10% over 6 months between July 1, 2018, and June 30, 2024, were included. The first dose of IGIV-C10% was assigned as index event. Patients were required to have 6-month continuous enrollment before and after index. Patients with a diagnosis of any condition that could have led to the prescription of IGIV-C10% (other than HGG secondary to CLL) at any point during the study period or who had received IgRT within 12 months prior to index were excluded. Patient demographics, clinical, and treatment characteristics were summarized with descriptive statistics. The proportion of patients with severe infections over the 6 months pre- and post-IGIV-C10% initiation was assessed and compared. Severe infections were defined as those considered as serious infection by the FDA's Sentinel Initiative (FDA, 2024), requiring injectable antimicrobials, or leading to hospitalization. A self-controlled study design was employed to assess the association between IGIV-C10% use and the odds of developing a severe infection. Generalized estimating-equation (GEE) logistic regression models adjusted for time-varying confounders, including cancer treatments during the pre- and post-index periods and index quarter and year to account for seasonality and temporal infection trends. Results: A total of 64 patients were included in the study. Mean (SD) age was 69.1 (9.1) years, and 59.4% were male; 42.2% of patients presented with hypertension and 20.3% had chronic obstructive pulmonary disease. Most common therapies during the study period were corticosteroids (N=59, 92.2%), kinase inhibitors (N=26, 40.6%), and B-cell monoclonal antibodies (N=24, 37.5%). The treatment patterns remained stable across the pre-IGIV-C10% and post-IGIV-C10%. Mean (SD) number IGIV-C10% doses received during the follow up was 6.0 (1.2) with an average dose per infusion of 25.5 (29.0) grams. Mean (SD) time between infusions was 4.5 (1.0) weeks. Both crude (OR: 0.31; 95% CI: 012, 0.78; p<0.01) and adjusted (OR: 0.17; 95%CI: 0.04, 0.72; p<0.05) analyses showed a statistically significant reduction in the odds of severe infection after IGIV 10% initiation, corresponding to a 83% reduction in adjusted odds for severe infection.Conclusions: The present real-world evidence study shows that monthly IGIV-C10% infusions are an effective therapy in reducing the odds of severe infections in patients with CLL and HGG.