Medically Reviewed by Brian Koffman,(MDCM )retired, MSEd
Bottom Line:
Serious infections are a key issue in CLL. Real-world data show they occur significantly less with zanubrutinib than with venetoclax and obinutuzumab.
Who Performed the Research and Where Was it Presented:
Dr. Nicole Lamanna led a group of researchers who presented SERIOUS INFECTIONS IN PATIENTS WITH CLL / SLL TREATED WITH COMBINATION VENETOCLAX AND OBINUTUZUMAB COMPARED WITH THOSE TREATED WITH ZANUBRUTINIB: A REAL-WORLD STUDY at the European Hematology Association, EHA’s Annual Congress 2025. A similar paper was presented at the Annual Meeting in 2025 of ASCO, the American Society of Clinical Oncology.
Background:
All chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL) patients are immunocompromised, leading to a higher risk of serious and even life-threatening infections. There are now multiple excellent choices of treatments that can knock down the CLL / SLL for a long time, making disease progression less of an issue for many. This positive development is now making infection risk an increasingly significant cause of morbidity and mortality for all CLL patients. Treatments with lower risk could offer an advantage, especially for those who are at high risk of infections.
Methods and Objectives:
- This real-world study compared the incidence of serious infections over 12 months in patients with CLL / SLL treated either with fixed-duration venetoclax plus obinutuzumab (VenO) or continuous zanubrutinib.
- Patients diagnosed with CLL / SLL who received VenO from 2016 to 2022 or zanubrutinib from 2019 to 2023 were included.
- The primary aim was to determine whether continuous zanubrutinib therapy is associated with fewer serious infections compared to the fixed-duration VenO regimen in real-world use.
- Assessments were done at 12 and 18 months post-treatment initiation. Keep in mind that the venetoclax plus obinutuzumab combination is usually given as a one-year fixed-duration therapy, meaning that many patients would be off therapy at the 18-month assessment, while zanubrutinib is given continuously.
Results:
- A total of 2,104 patients with CLL / SLL received VO, and 2,650 patients received zanubrutinib.
- Zanubrutinib was associated with significantly fewer serious infections compared to venetoclax and obinutuzumab at both 12 and 18 months.
- At 12 months, serious infections were seen in:
- Zanubrutinib: 4.8%
- VenO: 7.9%
- This is a 57% higher risk in the VenO group at 12 months.
- At 18 months, the difference persisted:
- Zanubrutinib: 5.6%
- VenO: 10.1%
Discussion:
There are many factors to be considered when choosing a CLL / SLL therapy. A partial list would include:
- Patient preferences, other illnesses, risks, and medications
- Biomarkers
- CLL history and prior therapies
- Efficacy
- Side effects
- Convenience
- IV versus oral
- Limited duration versus continuous
- Need for monitoring and/or hospitalizations
- Cost and insurance coverage
For some patients, infection risk could be an important factor to consider. This study offers another critical data point to consider when making a treatment choice.
Sources:
Read more details at SERIOUS INFECTIONS IN PATIENTS WITH CLL / SLL TREATED WITH COMBINATION VENETOCLAX AND OBINUTUZUMAB COMPARED WITH THOSE TREATED WITH ZANUBRUTINIB: A REAL-WORLD STUDY. You can also access a similar ASCO abstract.
