Dr Ermann on BTK Inhibitor Selection in Treatment-Naive CLL

“Having multiple studies to come out and show similar findings [for zanubrutinib] helps cement that what we are seeing is real and tangible.”

Daniel Ermann, MD, an associate professor in the Division of Hematology and Hematologic Malignancies and the physician lead of the Chronic Lymphocytic Leukemia (CLL) Clinical Trials Program at Huntsman Cancer Institute, discussed the results of a retrospective, real-world study evaluating zanubrutinib (Brukinsa) and acalabrutinib (Calquence) in treatment-naive CLL, which were presented at the 2026 ASCO Annual Meeting.

Data from an unadjusted Cox model showed that time to next treatment (TTNT) was significantly improved with zanubrutinib (n = 5819) in comparison with acalabrutinib (n = 10,969; HR, 0.88; 95% CI, 0.79-0.97; P = .009), and this benefit was reflected in an benefit an inverse probability of treatment weighting (IPTW) adjusted model (HR, 0.89; 95% CI, 0.80-0.98; P = .020).Moreover, median overall survival (OS) was not reached in both groups of the study, although zanubrutinib was still found to have a statistically significant improvement vs acalabrutinib in the unadjusted (HR, 0.72; 95% CI, 0.62-082; P < .001) and adjusted (HR, 0.75; 95% CI, 0.65-0.86; P < .001) models. Respective OS rates at 18, 24, and 30 months were 94%, 92%, and 91% for zanubrutinib, compared with 93%, 91%, and 89% for acalabrutinib.

Adverse effects (AEs) such as neutropenia may be more common with acalabrutinib, whereas AEs like atrial fibrillation and hypertension may be more common with zanubrutinib, Ermann began. He also noted that despite increased rates of different AEs between each BTK inhibitor, acalabrutinib and zanubrutinib ultimately have comparable safety profiles. Ermann underscored that when 2 treatments share similar safety profiles, unpacking differences in efficacy is crucial.

Ermann highlighted the improved TTNT shown with zanubrutinib in the retrospective data. Ultimately, Ermann concluded by emphasizing that this retrospective study can help provide real-world tangible evidence for clinical practice in the absence of head-to-head prospective trials for these BTK inhibitors.