Results: Of 291 randomized pts (194 to Ven and 97 to Placebo), 33 pts were receiving ongoing treatment (28 with Ven and 5 with Placebo) as of the final OS analysis data cutoff (March 15, 2021). At a median follow-up of 45.6 months, there were 78 (40%) deaths in the Ven arm versus 36 (37%) in the Placebo arm. Updated PFS and OS among all pts and those with t(11;14) or high BCL2 expression are shown in the Table. Among all pts, the median PFS per investigator was 23.4 months in the Ven arm versus 11.4 months in the Placebo arm (HR, 0.58 [95% CI, 0.43–0.78]). In pts with t(11;14), the median PFS was 36.8 months in the Ven arm versus 9.3 months in the Placebo arm (HR, 0.12 [95% CI, 0.03–0.44]). In pts with high BCL2, the median PFS was 30.1 months in the Ven arm versus 9.9 months in the Placebo arm (HR, 0.37 [95% CI, 0.21–0.64]). Median OS was not reached in the Ven or Placebo arm among all pts (HR, 1.19 [95% CI, 0.80–1.77]), pts with t(11;14) (HR, 0.61 [95% CI, 0.16–2.32]), pts with high BCL2 (HR, 0.70 [95% CI, 0.32–1.51]), and pts with t(11;14) or high BCL2 (HR, 0.82 [95% CI, 0.40–1.70]).

The most common treatment-emergent adverse events (AEs) with Ven (versus Placebo) were diarrhea (60% versus 50%), nausea (38% versus 23%), and constipation (35% versus 31%). The most common Grade 3/4 AEs (Ven versus Placebo) were thrombocytopenia (16% versus 30%), neutropenia (23% versus 8%), pneumonia (19% versus 13%), anemia (16% versus 15%), and diarrhea (15% versus 11%). Serious AEs occurred in 57% of Ven- and 55% of Placebo-treated pts, with serious infections and infestations occurring in 35% and 29% of pts, respectively. Overall, 26% of pts in the Ven arm and 11% of pts in the Placebo arm experienced an AE leading to Ven or Placebo discontinuation. AEs led to 12 deaths in the Ven arm, with 9 of these deaths due to serious infection; an AE led to 1 death in the Placebo arm. A total of 16 (6%) treatment-emergent deaths occurred (14 [7%] with Ven and 2 [2%] with Placebo), with 3 of these deaths due to disease progression (2 [1%] with Ven and 1 [1%] with Placebo).

Venetoclax