Immunoglobulin use, survival, and infection outcomes in patients with chronic lymphocytic leukemia

Patients with chronic lymphocytic leukemia (CLL) often experience infections due to immune suppression and/or dysregulation. Hypogammaglobulinemia is a key contributor to immunosuppression in CLL, and immunoglobulin replacement therapy (IgRT) is commonly given to prevent infections. However, the benefit of IgRT in preventing serious infections in CLL remains unclear. This study aimed to describe IgRT treatment patterns in a large, real-world cohort of patients with CLL, and explore the association between IgRT and serious infections. We conducted a retrospective longitudinal study of linked hospital data, including 6217 patients with CLL between 2008 and 2022 in Victoria, Australia. Kaplan-Meier survival analyses were performed to estimate survival, infection incidence, and IgRT use. Cox survival analyses explored associations between infections and IgRT in patients receiving regular prophylactic IgRT. Over the 14-year follow-up, the monthly proportion of patients experiencing serious infections doubled, while the proportion of patients receiving any IgRT quadrupled. The median time to death from CLL diagnosis was 10 years, and patients with serious infections had a higher mortality rate (0.090 [95% confidence interval (CI), 0.074-0.110]) vs those without (0.008 [95% CI, 0.007-0.009]). In total, 753 patients (12.1%) received IgRT, and 524 (8.4%) received IgRT regularly. In patients who received regular IgRT, infection incidence was higher during periods of IgRT (0.056 [95% CI, 0.052-0.060]) compared with periods without IgRT (0.038 [95% CI, 0.035-0.042]). Serious infections were associated with not only IgRT initiation and reinitiation, but also cessation. Further research is needed to evaluate the causal relationship between IgRT and infections in this population.