Venetoclax consolidation deepens response and enables measurable residual disease-guided finite therapy in BTK inhibitor-treated chronic lymphocytic leukemia.

Continuous Bruton tyrosine kinase inhibitor (BTKi) therapy is effective in chronic lymphocytic leukemia (CLL) but rarely eradicates measurable residual disease (MRD) and commits patients to indefinite treatment. In this single-center, real-world series, venetoclax was added as consolidation in 8 patients on continuous BTKi with adverse events and persistent peripheral-blood MRD. Patients were predominantly high-risk (6 of 8 IGHV-unmutated; 1 TP53-mutated) and had received BTKi for a median of 35 months. MRD was measured by flow cytometry (sensitivity 10-5). At a median follow-up of 12 months, all had MRD reductions; 4 of 6 evaluable patients (66%) achieved undetectable MRD (<10-5), the 2 remaining on therapy being non-evaluable. Six completed the 12-month course and stopped all therapy; 1 later relapsed. Treatment was well tolerated: grade 4 neutropenia in 2 patients, no tumor lysis syndrome, and no treatment-related deaths. Venetoclax consolidation is feasible, deepens response, and enables MRD-guided finite therapy in BTKi-treated CLL.