P650: effectiveness of venetoclax according to the characteristics of patients with cll in monotherapy and combination with rituximab. interim analysis of real-life data from verone study

Background: After positive findings from clinicals trials on venetoclax (VEN) in the chronic lymphocytic leukemia (CLL), Aims: this study aimed to describe the treatment effectiveness and tolerability in routine medical practice. Methods: This non-interventional longitudinal study is conducted in adult patients starting a treatment with VEN for CLL, with a 48-month follow-up. This new analysis allowed estimating the rates of overall response (ORR, primary criterion evaluated by clinicians), progression-free survival (PFS), and overall survival (OS) 1 and 2 years after the first intake of VEN in patients with ≥1 follow-up visit, according to the use of VEN [monotherapy (MONO) or combination with rituximab (COMBO)] (evaluable populations), and to sub-groups (TP53 and/or del(17)p alteration or not, < or ≥75 years old, ≤1, 2 or ≥3 previous lines, previous treatment with ibrutinib or not). Results: Between March 2018 and March 2022, among the 345 included patients, 334 (227 MONO, 94 COMBO, and 13 non-rituximab combinations) started VEN for CLL (safety populations), 332 (including 225 MONO and 94 COMBO) met selection criteria (analysis populations), and 195 (including 121 MONO and 70 COMBO) were analyzed for treatment effectiveness (evaluable populations). The characteristics of the 332 analyzed patients were as follows: median age 74.0 years (41.0-91.0), male gender 67.6%, ECOG ≥2 15.9%, median CLL duration 8.8 years (0.0-29.8), TP53 and/or del(17)p alteration 41.7% (123/295), median number of previous lines 2 (1-9), previous treatment with ibrutinib 57.5%. MONO and COMBO patient characteristics were similar. For this analysis, the median follow-up durations of MONO and COMBO patients were 28.4 and 24.3 months, respectively. In evaluable MONO patients, ORR was 88.4% [95% IC 81.5%-93.0%] at 1 year and 91.7% [85.5%-95.5%] at 2 years, with no difference according to patient sub-groups (ORR ≥83.3% at 1 year and ≥89.1% at 2 years). Similar results were observed in COMBO patients: ORR of 90.0% [80.8%-95.1%] at 1 year and 94.3% [96.2%-97.8%] at 2 years, with no differences according to patient sub-groups (ORR ≥84.2% at 1 year and ≥88.5% at 2 years). In MONO and COMBO patients, respective 1-year PFS rates were 84.6% [76.3-90.1] and 87.2% [76.0-93.4], PFS rates at 2 years were 71.7% [60.6-80.2] and 77.9% [64.9-86.6], with no difference according to patient and disease characteristics. OS rates were 88.8% [81.5-93.4] and 92.9% [83.7-97.0] at 1 year, and 79.6% [70.2-86.3] et 80.6% [68.0-88.7] at 2 years, and similar according to subgroups. Serious adverse events (SAEs) were reported in 45.8% of MONO patients et 45.7% of COMBO patients (SAEs related to VEN: 18.5% et 17.0% including 4 fatal events in 3 MONO patients: deterioration of the general status, ascites and hepatic failure, death with no precision). Over the ramp-up period, 8.8% of MONO patients and 9.6% of COMBO patients experienced tumor lysis syndrome which led to VEN discontinuation in 1.8% and 1.1% of patients Summary/Conclusion: These real-life data confirm the efficacy of VEN with or without rituximab in a population of patients with relapsed CLL less selected than those of clinical trials, with no difference found according to the main characteristics of the disease. No new toxicity signals were identified. Keywords: Chronic lymphocytic leukemia