Abstract

Background/Objectives: Covalent Bruton’s tyrosine kinase inhibitors (cBTKis) and the BCL-2 inhibitor venetoclax (VEN) have largely replaced traditional chemotherapy in clinical guidelines for frontline treatment of chronic lymphocytic leukemia (CLL). However, real-world evidence comparing these therapies on key outcomes remains limited. This study examined overall survival (OS) and time to next treatment (TTNT) among U.S. Medicare beneficiaries initiating frontline CLL therapy. Methods: In this retrospective study using 2016–2023 national 100% Medicare fee-for-service claims, we identified 10,949 patients aged ≥65 who initiated CLL treatment between June 2019 and December 2022. Patients received VEN-based regimens (n = 1503), cBTKi-based regimens (n = 5956), or other regimens (n = 3490). Results: Kaplan-Meier analyses showed superior OS for VEN-based regimens compared with cBTKi-based regimens and other regimens; three-year survival was 77% for VEN, 67% for cBTKis, and 62% for other regimens. In Cox regression models, cBTKis (hazard ratio [HR] 1.48, 95% CI 1.31–1.67) and other therapies (HR 1.66, 95% CI 1.47–1.89) were associated with worse OS relative to VEN. TTNT results also favored VEN; the percentage of patients with no evidence of second-line treatment at 3-years higher for VEN-based regimens (86%) compared to cBTKi-based regimens (69%) and other regimens (52%), despite similar follow-up times (median [months] VEN = 26.6, cBTKis = 26.2, Other = 21.8). cBTKis (HR 2.69, 95% CI 2.23–3.26) and other regimens (HR 6.47, 95% CI 5.32–7.86) were associated with a greater hazard for subsequent treatment relative to VEN. Conclusions: Our study demonstrates better survival and reduced need for subsequent treatment with VEN in patients with CLL treated in the frontline setting.

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