Immunoglobulin replacement therapy did not lead to a reduction in the risk for serious infections leading to hospitalizations for patients with chronic lymphocytic leukemia (CLL), according to the results of a real-world Australian cohort study published in Blood Advances. This finding is at odds with the increased clinical use of immunoglobulin therapy for patients with CLL to try to reduce infection risks.
“This is the first large, real-world study to follow patients with CLL who are regularly receiving immunoglobulin replacement,” stated 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.”
Study Methods and Rationale
Patients with CLL often experience infections as a result of immune suppression and/or dysregulation of antibodies. Immunoglobulin replacement therapy is typically given prophylactically to these patients as a means to avoid infections. However, it has previously been unclear whether immunoglobulin is actively preventing serious infections.
The study authors conducted a retrospective longitudinal study based on linked hospital data from the Victorian Cancer Registry, Death Index, and Admitted Episodes Data Set of 6,217 adults with CLL who were diagnosed between 2008 and 2022 in Victoria, Australia. They analyzed the associations among infection incidence, survival, and immunoglobulin replacement therapy use.
“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,” said study author Erica Wood, AO, MD, Professor at Monash University in Australia, where the cost of immunoglobulins are fully subsidized by the government. “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.”
Key Study Findings
The patients were followed for 14 years. During this time, the monthly rate of patients with serious infections doubled (from 1.9% to 3.9%) and the rate of immunoglobulin therapy quadrupled (from 2% to 8.8%). The median time to death from diagnosis of CLL was about 10 years, but patients with serious infections had a higher mortality rate (0.090; 95% confidence interval [CI] = 0.074–0.110) compared with those who did not have serious infections (0.008; 95% CI = 0.007–0.009).
A total of 12.1% of assessed patients received at least one dose of immunoglobulin replacement therapy at any time, and 8.4% received it regularly. Among the patients who received any immunoglobulin replacement therapy, 45.9% died during follow-up, with a median survival of about 6 years.
Regular immunoglobulins were received for 1 to 5 years in 46.9% of these patients, and 23.5% received regular immunoglobulin therapy for more than 5 years. Those receiving regular immunoglobulin therapy had higher infection rates while receiving the therapy (0.056; 95% CI = 0.052–0.060) compared with times they were not receiving immunoglobulin therapy (0.038; 95% CI = 0.035–0.042). Serious infections were associated with immunoglobulin replacement therapy initiation, re-initiation, and even cessation.
“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,” said Dr. Wood. “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.”
“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,” said Ms. Carrillo de Albornoz.
The study authors noted a need to further evaluate the relationship between immunoglobulin replacement therapy and infections in patients with CLL.
Disclosure: For full disclosures of the study authors, visit ashpublications.org.
