A large retrospective study of chronic lymphocytic leukemia (CLL) patients has challenged the effectiveness of immunoglobulin replacement therapy (IgRT) in preventing serious infections, raising important questions about current treatment practices and healthcare resource allocation.
The research, published in Blood Advances, analyzed data from 6,217 CLL patients diagnosed in Victoria, Australia, between January 2008 and December 2022. Of these patients, 753 (12.1%) received at least one dose of IgRT during the follow-up period, while 5,464 (87.9%) received none.
Infection Rates Increase Despite Treatment
Contrary to expectations, the study found that serious infections requiring hospitalization doubled from 1.9% to 3.9% during the study period, despite increasing use of immunoglobulin therapy. Among patients receiving IgRT regularly, infection frequency was significantly higher during treatment periods compared to off-treatment intervals (0.056 vs. 0.038 infections per person-month, respectively).
"This is the first large, real-world study to follow patients with CLL who are regularly receiving immunoglobulin replacement," said lead study author Sara Carrillo de Albornoz, health economist and PhD candidate at Monash University in Australia. "Given its high cost and variable use in clinical practice, this is a critical issue from a policy, economic, and clinical perspective."
Treatment Patterns and Survival Outcomes
The use of IgRT increased steadily among surviving patients over the 14-year period, rising from 2% in the first year post-diagnosis to 8.8% by year 14. Among patients who started IgRT, 46.9% remained on treatment for one to five years, while 23.5% continued for more than five years.
The mortality data revealed concerning patterns. Nearly half (45.9%) of the 753 patients who started IgRT died during the follow-up period, with a median survival time of approximately six years following treatment initiation. The 30-day mortality rate per person-month was markedly higher for patients hospitalized for serious infections within the month prior to starting IgRT compared with those without recent infections (0.090 vs 0.008).
Treatment Initiation Patterns
The study revealed 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.
Clinical and Economic Implications
Study author Erica Wood, professor at Monash University, emphasized the need for updated evidence: "Many of the studies supporting the use of immunoglobulins to reduce infections in patients with blood cancers date back over thirty years, and the treatment for CLL has advanced significantly since then. 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."
The therapy's high cost is driven by its complex manufacturing process and frequent administration schedule. In Australia, immunoglobulin therapy is fully subsidized by the government, but in other countries including the United States, the financial burden can be significant for patients and healthcare systems.
Study Limitations and Future Research
The researchers acknowledged several limitations of their retrospective analysis, including potential selection bias and incomplete data regarding clinical prognostic factors, disease severity, and cancer treatment details. Notable baseline differences existed between patient subgroups, particularly those receiving regular versus intermittent IgRT.
"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," Carrillo de Albornoz stated. "Although there are criteria for access to government-funded therapy in this population in Australia, clear clinical guidelines are lacking."
The research team is conducting follow-up investigations, including a clinical trial comparing immunoglobulins and antibiotics for infection prevention in patients with CLL, non-Hodgkin lymphoma, and multiple myeloma, as well as studies examining the economic burden of immunoglobulin use and serious infections among individuals with hematologic malignancies.
