Impact Of Premature Venetoclax (Ven) Discontinuation/Interruption On Outcomes In Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (Cll): Phase Iii Murano Study Results.

8028 Background: Ven + rituximab (VenR) has a manageable safety profile and improves survival in patients (pts) with R/R CLL, but discontinuation/interruption is frequent. We present new data from the Phase III MURANO study on the impact of Ven early discontinuation/interruption on outcomes in pts with R/R CLL. Methods: Time-dependent Cox proportional hazards regression models, stratified by 17p deletion and risk status, evaluated the impact of Ven discontinuation/interruption on investigator-assessed PFS and OS. Analyses were performed retrospectively (without type-1 error control) in intent-to-treat pts with R/R CLL from the fixed-duration VenR arm of MURANO (NCT02005471; data cut-off: May 8, 2019). Results: 140/194 pts (72%) in the VenR arm completed 2 years of therapy. Early discontinuation occurred in 54/194 (28%) pts (adverse events [AEs]: 29, disease progression [PD]: 12, withdrawal: 5, physician decision: 3, death: 2, other: 2, non-compliance: 1). Median Ven durations for pts discontinuing due to AEs and PD: 11.3 (0.5–24.6) and 17.1 (4.6–25.1) months, respectively (p = 0.08). Inferior PFS was observed in pts who discontinued Ven early for any reason except PD or due to AEs, versus those who completed therapy (Table). Greater cumulative Ven exposure significantly reduced risk of a PFS/OS event (PFS: HR 0.93, 95% CI 0.88–0.99, p = 0.0168; OS: HR 0.85, 95% CI 0.79–0.92, p < 0.0001). Treatment interruption for AEs occurred in 134/194 (69%) pts, most commonly due to neutropenia (84/194; 43%), per protocol requirements. Median duration of interruption: 9 (1–93) days. Treatment interruption, regardless of duration, had no impact on PFS or OS (Table). 36 (19%) pts with interruptions later discontinued Ven. Conclusions: In MURANO, early Ven discontinuation was associated with suboptimal outcomes; Ven interruption was not. These data highlight the importance of effective control of toxicity to realize the full benefit of VenR treatment. Clinical trial information: NCT02005471 . [Table: see text]