e18616 Background: Bruton tyrosine kinase inhibitors (BTKi) and venetoclax-based regimens have transformed the frontline management of chronic lymphocytic leukemia (CLL). BTKi are typically administered continuously, whereas venetoclax offers a fixed-duration, time-limited regimen. Real-world comparative effectiveness data between these treatment strategies remain limited. Methods: We performed a retrospective analysis using the TriNetX database, including patients aged ≥18 years diagnosed with CLL. Patients were divided into two cohorts based on the first-line therapy with either a BTKi (ibrutinib, acalabrutinib, or zanubrutinib, plus obinutuzumab) (BTKi group) or VenG (venetoclax plus obinutuzumab) (VenG group). Propensity score matching (PSM) was performed to balance baseline demographics. The primary outcome was 3-year overall survival (OS). Secondary outcomes included the rate of complete response (CR), all-cause intensive care unit (ICU) admission, atrial fibrillation, major bleeding, infection, and tumor lysis syndrome (TLS). Outcomes were analyzed using Kaplan-Meier survival estimates and measures of association. Results: Baseline characteristics were well-balanced following PSM. A total of 732 patients were included in each group. The mean age at index was 69.8 ± 9.8 years in the VenG group and 69.8 ± 11 years in the BTKi group. Males comprised 66.1% of the VenG group and 64.8% of the BTKi group, while females accounted for 33.9% and 35.2%, respectively. The majority of patients were White (81.3% in the VenG group and 81.1% in the BTKi group), followed by African American (8.9% vs 8.7%) and Asian (1.9% vs 1.6%). BTKi exposure included acalabrutinib (n = 351), ibrutinib (n = 343), and zanubrutinib (n = 82). VenG use was associated with a statistically significant improvement in 3-year OS compared to the BTKi group (p < 0.0001), with a hazard ratio (HR) of 0.54 (95% CI: 0.41–0.71). CR were more frequently observed in the VenG group compared to the BTKi group (17.4% vs. 9.4%, p < 0.0001). There were also significant differences between groups in the rate of major bleeding (4.5% vs. 7.4%, p = 0.0275). However, the VenG group showed a higher incidence of TLS (5.8% vs. 3.1%, p = 0.0153). There was no significant difference in rates of all-cause ICU admission (7.5% vs. 9.3%, p = 0.2287), atrial fibrillation (7.3% vs. 7.9%, p = 0.6949), and infection (19.9% vs. 17.3%, p = 0.2905). Conclusions: In this study, VenG therapy was associated with significantly improved OS and higher CR rates compared with continuous BTKi therapy. VenG also demonstrated lower rates of major bleeding, while rates of ICU admission, atrial fibrillation, and infection were comparable. The higher incidence of TLS with VenG highlights the importance of risk stratification and prophylactic measures. Overall, the results support the VenG regimen as an effective frontline treatment option.
Ng et al. (Thu,) studied this question.