Clinical Journey and Immunoglobulin-Replacement Therapy Treatment Patterns in Chronic Lymphocytic Leukemia Patients
Authors: Jordan James , Haviland Miriam , Gomez-Ulloa David , Vainorius Enrikas , Whyms Dermot , Runken M. Chris 
Published: December 2024

Introduction: Patients with Chronic Lymphocytic Leukemia (CLL) are at risk of secondary immunodeficiency (SID), which can be caused by CLL itself as well as by its treatments. IgG deficiency or hypogammaglobulinemia is a subtype of SID that leads to higher risk of infections and constitutes one of the major causes of morbidity and mortality in these patients (Allegra et al. Front Immunol 2021). Clinical guidelines recommend screening IgG levels at CLL diagnosis, before starting immunosuppressive therapies, and regularly monitoring levels every 3 -to-12 months thereafter, since immunoglobulin replacement therapy (IgRT) is recommended in CLL patients with HGG and severe, recurrent, or unusual infections (Otani et. al. J Allergy Clin Immunol 2022). Although IgRT effectiveness in SID patients has been previously assessed, IgG testing and IgRT patterns are not fully understood. The present study aims to assess IgG testing and IgRT treatment patterns in CLL patients presenting with recurrent or severe infections.

Methods: A retrospective cohort study utilizing data from the PharMetrics Plus database, a database of insured US patients, from January 2015 through September 2023, was implemented. Patients diagnosed with CLL (ICD-10 code C91.1) who experienced either 1) one severe or 2) two non-severe infections over 12 months (recurrent infections), after CLL diagnosis were included. Index event was defined as the earliest of either 1) the start of the first severe infection or 2) the start of the second non-severe infection. Severe infections were defined as those presenting an encounter with an ICD-10 code considered serious by FDA's Sentinel Initiative (FDA, 2024), requiring IV or IM antimicrobials, or leading to a hospitalization. Only patients with at least 18 months of continuous insurance coverage (≥12 months pre- and ≥6 months post-index) were included. In order to exclude any IgRT use other than for SID, patients with a documented diagnosis that may require IgRT or IgG immunomodulation therapy at any point in patient record or who received IgRT between CLL diagnosis and index were excluded. Data on demographic, clinical and treatment characteristics, IgG testing, presence of HGG (ICD-10 D80.3, D80.1, or D84.9) and use of IgRT were gathered. All analyses were stratified based on whether the patient received IgRT or not.

Results: A total of 12,932 CLL patients presenting with severe or recurrent infections were included; 446 (3.4%) received gRT (IgRT users) and 12,486 (96.6%) did not receive IgRT(non-IgRT users). Mean (SD) age [63.8 (10.3) vs. 64.8 (11.7)] and sex distribution [male 259 (57.8%) vs. 7,181 (57.0%)] was similar among groups. Antibiotic use was more common across IgRT users prior to index [61 (13.7%) vs 1,261 (10.1%)], whereas the opposite trend was observed post-index [125 (28.0%) vs 3,651 (29.2%)]. IgG levels were tested in 37.9% of IgRT users and 24.7% of non-IgRT users prior to index. After index, the proportion of patients for whom IgG levels had been tested increased, particularly among IgRT users [70.8%) vs 30.0%]. The proportion of patients presenting with HGG was higher among IgRT patients both pre- [69 (15.4%) vs 482 (3.8%)] and post-index [246 (55.2%) vs 1,371 (11.0%)]. Among patients treated with IgRT, mean (SD) number of doses over 3-, 6-, and 12-month follow up were 2.9 (1.4), 4.5 (2.4) and 7.5 (4.9). Mean (SD) time between IgRT doses was 6.1 (3.8), 9.3 (7.8) and 14.0 (14.9) weeks, respectively.

Conclusions: The present real world cohort study exposes the low proportions of IgG testing and IgRT use among CLL patients with severe or recurrent infections. In addition, among patients who received IgRT, this study also seems to uncover suboptimal IgRT use with long intervals between doses.