Zanubrutinib Linked to Lower Infection Risk Than Venetoclax Plus Obinutuzumab in Real-World CLL/SLL Study

Patients with chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) treated with venetoclax (Venclexta; AbbVie Inc) plus obinutuzumab (Gazyva; Genentech) had a higher risk of serious infections compared with those treated with zanubrutinib (Brukinsa; BeiGene), according to findings from a real-world study. The study data, published in the Journal of Clinical Oncology, suggest that zanubrutinib could be considered an alternative treatment option to venetoclax and obinutuzumab for patients with a higher risk of infections.¹

Close-up of leukemia cells | Image Credit: © Brighting Collection - stock.adobe.com

CLL/SLL remains incurable but is often manageable, with modern therapies pushing the 5-year overall survival rate above 90%. Treatments such as monoclonal antibodies (eg, obinutuzumab), Bruton tyrosine kinase (BTK) inhibitors (eg, zanubrutinib), and BCL-2 inhibitors (eg, venetoclax) have significantly improved outcomes and transformed the treatment landscape for CLL/SLL. However, patients with CLL/SLL typically have a higher risk of serious infection due to their compromised immune systems, raising concerns about the association between CLL/SLL-directed therapies and serious infection risks.^1,2

To better understand this relationship, researchers assessed 4754 patients with CLL/SLL who were treated with either venetoclax and obinutuzumab from April 2016 to August 2022 (n = 2104) or zanubrutinib from November 2019 to August 2023 (n = 2650). Given the fundamental differences between time-limited venetoclax and obinutuzumab and continuous therapies, rates of serious infections were assessed at both 12- and 18-month follow-up periods following treatment initiation.¹

Serious infections were defined as those requiring intravenous antibiotics or antivirals within 15 days of hospitalization. Inverse probability of treatment weighting (IPTW) with Cox proportional hazard models was used to adjust for baseline characteristics, including age, sex, race, and ethnicity, Charlson Comorbidity Index (CCI), and geographic region, and to estimate hazard ratios (HRs) comparing the 2 cohorts.¹

At 12 months, 7.9% of patients in the venetoclax and obinutuzumab cohort experienced serious infections and had a significantly higher risk of serious infections compared with patients treated with zanubrutinib (HR, 1.57; 95% CI, 1.23–1.99). At 18 months, the incidence of serious infections rose to 10.1%. Kaplan-Meier curves showed a consistently higher proportion of serious infections throughout the follow-up period.¹

Comparatively, patients who received zanubrutinib had superior outcomes to those treated with venetoclax and obinutuzumab. At 12 months, 4.8% of patients experienced serious infections, with the incidence increasing to 5.6% by 18 months.¹

These data, which were presented at the 2025 American Society of Clinical Oncology Annual Meeting, provide more guidance for clinical oncology pharmacists and oncologists when treating patients with a higher risk of serious infections. The results suggest that venetoclax plus obinutuzumab is a guideline-recommended treatment with established efficacy; zanubrutinib may offer a more appropriate treatment option for certain patients.

REFERENCES

1. Colasurdo J, Zhou L, Ali A, et al. Serious infections in patients with CLL/SLL treated with combination venetoclax and obinutuzumab compared with those treated with zanubrutinib: A real-world study. J Clin Oncol. May 28, 2025. Doi:10.1200/JCO.2025.43.16_suppl.e19026

2. Gerlach A. Targeted therapies transform CLL Ccare: Inside the era of BTK and BCL2 inhibitors. Pharmacy Times. April 29, 2025. Accessed July 9, 2025. https://www.pharmacytimes.com/view/targeted-therapies-transform-cll-care-inside-the-era-of-btk-and-bcl-2-inhibitors