Infection Rate More Than Doubles in CLL/SLL Accompanied by Secondary Immunodeficiency Disease

Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) plus a secondary immunodeficiency disease (SID) were 70.1% more likely to have an infection compared with 30.4% for CLL/SLL patients without SID, according to a retrospective database study in the Annals of Hematology.1

A subpopulation of patients with CLL/SLL and secondary immunodeficiency disease carry increased infection risks | image credit: sdecoret - stock.adobe.com

Overall survival was 12.3 months for SLL patients vs 16.9 months for CLL/SLL individuals without an SID. Patients with SID faced a 39.8% risk of contracting a severe bacterial infection and a 27.7% risk for hospitalization due to infection, meanwhile, patients withCLL/SLL with no SID had a9.2% and 5.8% risk for the same outcomes, respectively. Slightly more than a quarter of patients with SID were hospitalized for an infection at least once for an average of roughly 10 days. Patient data were taken from 2015 to 2020.

The mean number of any type of infection after a 12-month follow-up in the SID group was 8.4, and 7.8 for severe infections. However, infections lasting more than a day were logged each day with the same diagnostic code, making it possible, especially with severe infections, that a single infection was recorded multiple times.

Antibiotic use was more strongly associated with the SID group, corresponding to 83% of anti-infective claims vs 46% for the no-SID group. Overall, roughly 86% of the SID group had 1 or more claims for an anti-infective vs nearly 49% for patients without SID. The SID group was also linked to more prescription fills, with nearly 25, compared with about 13 for patients without SID.

Identification of SID in CLL/SLL and treatment are inadequate, the authors claim. At present, typical management for SID in CLL/SLL includes serum immunoglobulin G (IgG) monitoring, immunoglobulin replacement therapy (IgRT) and antibiotics.

Patients with CLL/SLL facing the highest odds of infection were those with SID who had also received image-guided radiation therapy (IGRT). Roughly one-third of patients receiving IgRT had at least 1 hospitalization because of an infection compared with nearly 1 in 5 for patients without IgRT. The study did not include IgRT dose or how many infusions the patient had received.

More guidance is needed regarding optimal IgRT dosing, according to the study. A separate trial referenced by the study found that IgRT can reduce infections in CLL patients with SID and a history of infections, but nearly one-third of these patients did not respond to IgRT. When the IgRT dose was raised in these patients, from 18g to 24g, most patients did not experience infection over a 1-3-month period.2

In the current study, IgRT did not affect OS, but patients who received IgRT had a median survival rate of 12.8 months vs 12.3 months without IgRT. Patients in the IgRT group were less likely to maintain an IgG level of less than 5 g/L post-index. About three-quarters of IgRT-treated patients exhibited a rise in IgG serum levels to 5 or higher g/L over the follow-up period, vs 17.8% for the no-IgRT group.

About three-quarters of patients with SID and mature B-cell malignancies are prescribed IgRT that do not meet the European Medicines Agency’s recommendations for IgRT use in CLL/SLL with SID.

More research is needed around IgRT in SID, the authors conclude, and future studies should focus on how to best identify which patients with CLL/SLL are most at risk of developing SID.

“Increasing understanding of SID burden may help to improve outcomes in patients with CLL/SLL. Further research is needed to develop guidance for IgRT use and to assess the benefits of IgRT in this vulnerable population,” the authors write.

The higher risk for infection in CLL patients could be caused by “prolonged exposure to antigen,” which results in “an upregulation of T cell inhibitory receptors that become increasingly dysfunctional,” the authors write.

References

1. Siffel, C., Richter, J., Anderson-Smits, C. et al. Treatment patterns and burden of infection in patients with chronic lymphocytic leukemia and secondary immunodeficiency: a retrospective database study. Ann Hematol. 2024; 103, 4567–4580. doi:10.1007/s00277-024-05984-6
2. Freeman JA, Crassini KR, Best OG, et al. Immunoglobulin G subclass deficiency and infection risk in 150 patients with chronic lymphocytic leukemia. Leuk Lymphoma. 2013; 54:99–104. doi:10.3109/10428194.2012.706285