Infection Risk Factors in Patients with CLL on BTK Inhibitors

Authored by Ann Liu, PhD
Medically Reviewed by Brian Koffman, MDCM (retired), MSEd

The Bottom Line:

Patients with CLL on BTK inhibitor therapy develop mostly minor infections, but prior pneumonia and chronic obstructive pulmonary disease (COPD) were risk factors for developing severe infections.

Who Performed the Research and Where Was it Presented:

Dr. Francesco Autore from Gemelli University Hospital in Italy and colleagues presented the results at the American Society for Hematology (ASH) Annual Meeting in 2025.

Background:

Infections are a major concern for patients with chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL), because all patients with CLL / SLL are immunocompromised and have a hard time fighting off infections. Most patients with CLL / SLL are older adults, and as we age, immune function naturally tends to decline. Additionally, CLL / SLL is a cancer of the antibody-producing B cells, which causes further immune dysfunction. CLL / SLL patients are living longer, but even when their cancer is in remission, they are increasingly dying of infections, often a direct result of their impaired immunity. In this study, researchers looked at what factors might influence infection risk in patients with CLL treated with second-generation Bruton tyrosine kinase inhibitors (BTKi).

Methods and Participants:

This was a retrospective study using data from 15 different hematological centers. It included patients with CLL treated with second-generation BTKi acalabrutinib or zanubrutinib between 2019 and 2024.

Results:

• A total of 460 patients were included in the analysis, of which 324 received acalabrutinib, and 136 received zanubrutinib.
• The rates of non-COVID infections were similar for both the acalabrutinib (34%) and zanubrutinib (36%) groups, and about half of those infections were respiratory infections.
• Severe infections occurred in 13% of patients in the acalabrutinib group, and 10% of patients in the zanubrutinib group, and these infections included respiratory infections and sepsis.
• Causes of these infections included bacteria, viruses, and fungi.
• Significant predictors of developing severe infections were prior pneumonia (both groups) and chronic obstructive pulmonary disease (COPD, acalabrutinib group only).
• Risk factors for developing any infection included:
  • Acalabrutinib group: age, diabetes, COPD, impaired kidney function, prior lines of therapy, history of infections or pneumonia
  • Zanubrutinib group: diabetes, Rai stage, history of infections or pneumonia
• In the acalabrutinib group, 35% of patients discontinued treatment due to infections, and 25% discontinued treatment due to infections in the zanubrutinib group.
• The 5-year overall survival rate was 71% for the acalabrutinib group with 16 infection-related deaths.
• The 5-year overall survival rate was 80% for the zanubrutinib group with 4 infection-related deaths.
• COVID-19 infections occurred in 26% of patients in the acalabrutinib group and 13% of patients in the zanubrutinib group, with about half of these patients developing other infections.
• Three patients died from COVID-19 infections, all in the acalabrutinib group.

Conclusions:

Patients with CLL on BTK inhibitor therapy develop mostly minor infections at a moderate rate, with about one-third of patients developing an infection. Prior pneumonia and COPD were significant risk factors for developing severe infections. Patients with these specific risk factors may need closer monitoring or tailoring of their treatment plans to account for their increased risk of developing severe infections.

Links and Resources:

You can read the actual ASH abstract here: Chronic obstructive pulmonary disease and prior pneumonia as predictors of infectious risk in chronic lymphocytic leukemia patients receiving acalabrutinib or zanubrutinib: A seifem multicentre study

Take care of yourself first.

Ann Liu, PhD