Immunoglobulin Replacement Therapy Not Shown to Lower Serious Infection Risk in CLL

Regular treatment with immunoglobulin replacement therapy (IgRT) was not linked to a reduced risk of serious infections requiring hospitalization in patients with chronic lymphocytic leukemia (CLL), according to findings from a retrospective analysis published in Blood Advances.^1,2

The research showed that despite the use of IgRT increasing over time, the study population experienced a doubling (1.9% to 3.9%) in the rate of serious infections requiring hospitalization during the study period. Further, among patients treated regularly with IgRT, the frequency of infections during treatment periods was much higher compared with treatment intervals, at 0.056 vs. 0.038 infections per person-month, respectively.

Regarding mortality, nearly half (45.9%) of the 753 patients who started IgRT died during the follow-up period. The median survival time was about 6 years following the start of treatment. In line with these survival data for the entire study population, the 30-day mortality rate per person-month was markedly higher (0.090 vs 0.008) for patients hospitalized for a serious infection within the month prior to starting IgRT compared with patients who did not have a recent infection.

“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, stated in a press release. “Given its high cost and variable use in clinical practice, this is a critical issue from a policy, economic, and clinical perspective.”

“The cost of this therapy, its burden to patients, and the patterns of use and infection we observed are a clear call for better guidelines on the use of immunoglobulins,” added Carrillo de Albornoz.

Immunoglobulin Replacement Therapy Study Background

According to Carrillo de Albornoz et al CLL impairs the body’s ability to produce infection-fighting antibodies, leaving patients vulnerable to severe and potentially life-threatening infections. To help strengthen immune defense, immunoglobulin replacement therapy is commonly administered to increase antibody levels and lower the likelihood of infection.¹

Carrillo de Albornoz et al analyzed data from adults diagnosed with CLL in Victoria, Australia, between January 1, 2008, and December 31, 2022. Specifically, the researchers used linked information from the Victorian Cancer Registry, Death Index, and Admitted Episodes Dataset, which provided long-term hospital and mortality data. The cohort included 6217 patients, with 12.1% (753 patients) receiving at least 1 dose of IgRT during the follow-up period and 87.9% (5464 patients) receiving none. On average, patients were followed for 6.9 years.

Use of IgRT increased steadily among patients who survived over the 14-year period, rising from 2% in the first year post-diagnosis to 8.8% by year 14. During the study period, 35.2% of patients died. The median time to death was approximately 10 years following diagnosis.

Of those receiving ongoing IgRT, 46.9% remained on treatment for 1 to 5 years, while 23.5% continued for more than 5 years—depending on their duration of follow-up and survival.

The data also showed that serious infections were a key factor in initiating IgRT. Patients who experienced a serious infection began IgRT at a rate of 0.075 per person-month within 30 days of the infection, compared with a much lower rate of 0.001 per person-month among those without such infections.

Carrillo de Albornoz et al noted that their study's retrospective design presents several limitations, including the potential for selection bias and gaps in available data, particularly regarding key clinical variables such as prognostic indicators, disease stage, and details of cancer treatment. There were also notable baseline differences between patient subgroups that were compared, including patients receiving IgRT on a regular basis vs occasionally.

To build on these findings, Carrillo de Albornoz et al are conducting follow-up investigations, including a study comparing immunoglobulins and antibiotics for infection prevention in patients with CLL and other blood cancers, as well as research examining the economic burden of immunoglobulin use and serious infections among individuals with hematologic malignancies.

“Many of the studies supporting the use of immunoglobulins to reduce infections in patients with blood cancers date back over 30 years, and the treatment for CLL has advanced significantly since then,” study author Erica Wood, AO, MD, professor at Monash University, stated in the press release. “While immunoglobulins likely do benefit some patients, there remains a critical need to better understand the extent of that benefit, who is most likely to benefit, and how long these patients should be receiving treatment.”

REFERENCES:

1. Carrillo de Albornoz S, Zhang X, Arnolda R, et al. Immunoglobulin use, survival, and infection outcomes in patients with chronic lymphocytic leukemia [published online ahead of print July 30, 2025]. Blood Adv. doi:10.1182/bloodadvances.2025015867

2. Immunoglobulin Replacement Therapy Shows No Reduction in Serious Infections for Patients with CLL [press release]. American Society of Hematology. Published online July 31, 2025. Accessed August 6, 2025. https://tinyurl.com/2hvfhfa2