Immunoglobulin Replacement Therapy Fails to Lower Hospitalizations in CLL, Study Finds

Regular immunoglobulin replacement therapy (IgRT) was not associated with a reduced risk of infection-related hospitalizations in patients with chronic lymphocytic leukemia (CLL), according to data published in Blood Advances.¹

Immunoglobulin in IV | Image Credit: © Trsakaoe - stock.adobe.com

“This is the first large, real-world study to follow patients with CLL who are regularly receiving immunoglobulin replacement,” lead study author Sara Carrillo de Albornoz, health economist and PhD candidate at Monash University in Australia, said in a news release. “Given its high cost and variable use in clinical practice, this is a critical issue from a policy, economic, and clinical perspective.”²

Patients with CLL are at high risk of infection due to immune suppression or dysregulation caused by interruptions in antibody production. Hypogammaglobulinemia is a key contributor to immunosuppression, and IgRT is the standard treatment given to prevent infections; however, the true benefit of this approach in preventing serious infection is unknown.^1,2

Albornoz and her team performed a retrospective longitudinal study of linked hospital data in a large, real-world cohort of patients with CLL (n = 6217) between 2008 and 2022. They used Kaplan-Meier survival analyses to estimate survival, infection incidence, and IgRT use, while Cox survival analyses helped determine associations between infections and IgRT in patients receiving regular prophylactic IgRT.¹

Over the 14-year follow-up period, patients experiencing serious infections doubled. Meanwhile, the proportion of patients receiving any IgRT quadrupled. The proportion of patients receiving IgRT also increased from 2% to 8.8% by year 14. The median time to death from diagnosis was 10 years, and those with serious infections had a higher mortality rate (0.090; 95% CI 0.074–0.110) versus those without (0.008; 95% CI 0.007–0.009). About 35% of patients died (2191 of 6217).¹

Patients who had a serious infection were much more likely to begin receiving IgRT in the 30 days following their infection, at a rate of 0.075 per person-month (a unit that measures incidence per each person observed for a month), compared with just 0.001 per person-month for those without a serious infection. This was consistent across the study population. In total, about 12.1% of patients (n = 753) received IgRT, and 8.4% (n = 524) received IgRT regularly.¹

The incidence of infection was greater in patients receiving regular IgRT during IgRT periods (0.056; 95% CI: 0.052, 0.060) than during periods without IgRT treatment (0.038; 95% CI: 0.035, 0.042). Serious infections were associated with not only IgRT initiation and reinitiation but also cessation.¹

“We not only saw no reduction in infection rates or hospitalizations among patients receiving immunoglobulins, we found that many were on this therapy for extended periods of time,” study author Erica Wood, AO, MD, professor at Monash University, said in the news release. “It’s essential that we evaluate how long these patients remain on treatment and why to avoid unnecessary, prolonged, and expensive therapy of a product in limited supply internationally.”²

The findings suggest that regular IgRT does not reduce the risk of infection-related hospitalizations in patients with CLL, despite its widespread and increasing use. Instead, serious infections remained a major driver of both IgRT initiation and mortality throughout follow-up. These results underscore the need for more targeted strategies to prevent infections in this population and highlight the importance of reassessing when and for how long IgRT should be used, given its high cost and limited global availability.

REFERENCES

1. Albornoz De Carillo S, Zhang X, Arnolda R, et al. Immunoglobulin use, survival, and infection outcomes in patients with chronic lymphocytic leukemia. Blood Adv. July 30, 2025. doi.org/10.1182/bloodadvances.2025015867

2. Immunoglobulin Replacement Therapy Shows No Reduction in Serious Infections for Patients with CLL. American Society of Hematology. July 31, 2025. Accessed August 19, 2025. https://www.hematology.org/newsroom/press-releases/2025/igrt-shows-no-reduction-in-serious-infections-for-patients-with-cll