Real-world comparative effectiveness of first-line BTK inhibitors in chronic lymphocytic leukemia

Introduction Second-generation covalent Bruton tyrosine kinase inhibitors (cBTKi), acalabrutinib and zanubrutinib, are standard-of-care for treatment-naïve adults with chronic lymphocytic leukemia (CLL). However, real-world evidence remains limited.Methods This real-world analysis compared acalabrutinib and zanubrutinib using the IntegraConnect PrecisionQ de-identified electronic health record database, representing >3 million cancer patients across 500+ US sites. Patients initiated cBTKi between January 2020 and November 2023, with follow-up through 3 July 2024.Results This study included 473 patients; 184 zanubrutinib-treated patients matched to 289 acalabrutinib-treated patients by age and sex. Baseline characteristics were similar. Median time to discontinuation (TTD) for acalabrutinib was 29.5 months (95% confidence interval [CI] 21.2, not reached [NR]). Median TTD for zanubrutinib was NR, with significantly longer duration of treatment than acalabrutinib (adjusted hazard ratio [aHR]: 0.50, 95% CI 0.3–0.7; p < .01). The 12-month probability of remaining on treatment with zanubrutinib (83.3%) was higher than acalabrutinib (69.5%). Toxicity-related discontinuation was higher with acalabrutinib (10.7%) than zanubrutinib (5.4%). Median time to next treatment was 42.5 months for acalabrutinib (95% CI 33.2-NR) and NR for zanubrutinib (aHR 0.82; 95% CI 0.5–1.4).Conclusion Zanubrutinib demonstrated longer treatment persistence and fewer discontinuations attributed to toxicity during chart abstraction than acalabrutinib in treatment-naïve CLL.