Dose modifications, discontinuation patterns and PFS of zanubrutinib in 410 CLL/SLL patients – a nationwide real-world cohort

Zanubrutinib is a new Bruton’s tyrosine kinase inhibitor (BTKi) with increased BTK specificity and fewer off-target effects. Data from recipients of clinical trials are limited. We interrogated data from 410 subjects with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) receiving zanubrutinib from September 2016 to March 2024 at regional centers. Outcomes studied included duration of treatment, reasons for discontinuation, frequency of dose reductions, previous BTKi exposure, progression-free survival (PFS), and survival. A total of 410 patients were analyzed for efficacy with a median follow-up of 20.7 (interquartile range [IQR], 8.6–34.9) months. Therapy was discontinued in 76 subjects (18.5%) because of disease progression ( n = 32; 7.8%), subject preference ( n = 25; 6.1%), adverse events (AEs; n = 15; 3.7%), and death of unknown cause ( n = 4; 1.0%). Forty-six subjects (11.2%) had ≥ 1 dose reduction mainly because of AEs ( n = 17; 4.1%) or patient preference ( n = 26; 6.3%). The 3-year PFS was 91.6% (95% CI, 83.8–95.8%) in subjects receiving zanubrutinib as initial therapy and 83.2% (95% CI, 74.6–89.1%) in those receiving it later. In the dose reduction group ( n = 46), no progression or death was observed after dose reduction, with a median follow-up of 10.9 (IQR, 6.4–25.6) months from the first dose reduction. Among 54 patients who switched to zanubrutinib from other BTKi without evidence of disease progression, 32 switched to zanubrutinib due to AEs, 19 due to patient preference, and 4 for unknown reasons; the reasons for switching were not mutually exclusive. The median duration of zanubrutinib treatment was 10.1 months among patients who switched due to AEs and 16.5 months among those who switched due to patient preference. The PFS was not reached in either group. Our study provides real-world evidence regarding treatment patterns, dose modifications, discontinuation, switching, and clinical outcomes among patients with CLL/SLL treated with zanubrutinib in routine clinical practice. This study is registered with ClinicalTrials.gov, NCT06489184. URL: https://clinicaltrials.gov/study/NCT06489184 . Date of registration: 2024-07-05.