Cytoreduction-Adapted Outpatient Venetoclax Ramp-Up in CLL/SLL: A Real-World Pilot Study

Venetoclax-based therapy is effective in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), but tumor lysis syndrome (TLS) risk necessitates a resource-intensive five-week dose ramp-up with intravenous hydration, frequent laboratory monitoring, and clinic-based observation, creating logistical barriers particularly in community settings. We conducted a single-center, IRB-approved retrospective pilot study of 30 patients with CLL/SLL who underwent a cytoreduction-adapted, IV-free outpatient venetoclax ramp-up with reduced laboratory monitoring between 2023 and 2026. All patients received cytoreductive therapy—predominantly single-agent BTKi—and met protocol-defined low-tumor-burden criteria (ALC < 20 × 109/L, lymph nodes < 5 cm, no splenomegaly, CrCl > 45 mL/min) before venetoclax initiation. Venetoclax was self-administered at home with laboratory monitoring reduced to a single approximately 12-h post-dose assessment per dose-escalation week. Median age was 71 years; 80% had received ≥2 prior therapy lines, and 37% had high-risk cytogenetics. Monitoring compliance was 100%. No laboratory or clinical TLS, IV hydration, hospitalizations, dose interruptions, treatment discontinuations, or deaths occurred during ramp-up. These pilot data support the feasibility and early safety of simplified outpatient venetoclax initiation in adequately cytoreduced patients and warrant prospective multicenter validation.