Contributions
Abstract: EP646
Type: E-Poster Presentation
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
The efficacy and tolerability of venetoclax (V), a first-in-class selective oral B-cell lymphoma 2 (BCL-2) inhibitor, were shown in previous clinical trials for patients with chronic lymphocytic leukaemia (CLL). However, real-world data having assessed V in non-selected CLL patients are limited.
Aims
This French observational, prospective ongoing study aims to describe the effectiveness and tolerability of V in a real-life setting, and the V use in routine clinical practice.
Methods
This prospective non-interventional study is conducted in adult patients starting V for CLL (NCT03415035). This first analysis was performed in patients treated with V monotherapy, 16 months after the first inclusion in the study. The Overall Response Rate (ORR), and the Progression-Free Survival (PFS) were estimated at 1 year after V start in patients with at least one follow-up visit (evaluable population).
Results
From March 2018 to June 2020, 158 patients, included in 60 centres, started V monotherapy for CLL and were retained in the safety population, 153 met all the selection criteria (analysed population), and at date 62 entered the evaluable population. In the analysed population (n=153), baseline patient and CLL characteristics were as follows: mean age, 72.1±10.3 years; male, 69.3%; ECOG ≥2, 17.9%; ≥1 comorbidity, 86.9%; median CLL duration, 8.3 years (range: 0.1 - 29.4); prior CLL therapy, 96.7% (median number in pre-treated patients: 2, range 1 – 9; 1/2/≥3 prior treatment lines, 19,6%/31,8%/48,6%; including chemo-immuno-therapy 83.7%, B-cell receptor inhibitors 73.9%; Del(17p), 15.0%; TP53 mutation, 12.4%.Prior to the first V intake, preventive measures were taken in most patients (hospitalisation 86.1%, hydration 86.7%, antihyperuricemic prophylaxis 72.8%, laboratory assessments 62.7%). The median duration of the ramp-up period was 5.0 weeks (range 1.0 – 23.9), and 72.8% reached the recommended daily dose of 400 mg at the moment of the analysis. In the 62 patients of the evaluable population, the 1-year ORR was 85.5% [95% CI 76.7% - 94.3%]. Considering the median follow-up of patients of 13.1 months, the 1-year estimate for PFS was 80.2% [95% CI 68.8% - 88.6%]. Overall, 81.0% of the 158 patients of the safety population experienced adverse events [AEs, mainly as neutropenia (43.0%) and diarrhoea (23.4%)], 58.2% ≥grade 3 AEs, 45.6% serious AEs (SAEs), and 19.6% V-related SAEs. Three patients experienced 4 fatal V-related AEs (deterioration of the general status, ascites, hepatic failure, and unknown cause at home). Over the ramp-up period, 16 patients (10.1%) experienced tumour lysis syndrome (assessed as serious in 3 patients, 1.9%; leading to treatment discontinuation in 4 patients, 2.5%).
Conclusion
Our first real-world data show that V monotherapy is effective in non-selected pre-treated CLL patients, with similar outcomes as compared to clinical trials. Early safety data are reassuring with few tumour lysis syndromes leading to treatment discontinuation during the ramp-up period. Further results are expected next year.
Keyword(s): BCL2, Chronic lymphocytic leukemia, Targeted therapy
Abstract: EP646
Type: E-Poster Presentation
Session title: Chronic lymphocytic leukemia and related disorders - Clinical
Background
The efficacy and tolerability of venetoclax (V), a first-in-class selective oral B-cell lymphoma 2 (BCL-2) inhibitor, were shown in previous clinical trials for patients with chronic lymphocytic leukaemia (CLL). However, real-world data having assessed V in non-selected CLL patients are limited.
Aims
This French observational, prospective ongoing study aims to describe the effectiveness and tolerability of V in a real-life setting, and the V use in routine clinical practice.
Methods
This prospective non-interventional study is conducted in adult patients starting V for CLL (NCT03415035). This first analysis was performed in patients treated with V monotherapy, 16 months after the first inclusion in the study. The Overall Response Rate (ORR), and the Progression-Free Survival (PFS) were estimated at 1 year after V start in patients with at least one follow-up visit (evaluable population).
Results
From March 2018 to June 2020, 158 patients, included in 60 centres, started V monotherapy for CLL and were retained in the safety population, 153 met all the selection criteria (analysed population), and at date 62 entered the evaluable population. In the analysed population (n=153), baseline patient and CLL characteristics were as follows: mean age, 72.1±10.3 years; male, 69.3%; ECOG ≥2, 17.9%; ≥1 comorbidity, 86.9%; median CLL duration, 8.3 years (range: 0.1 - 29.4); prior CLL therapy, 96.7% (median number in pre-treated patients: 2, range 1 – 9; 1/2/≥3 prior treatment lines, 19,6%/31,8%/48,6%; including chemo-immuno-therapy 83.7%, B-cell receptor inhibitors 73.9%; Del(17p), 15.0%; TP53 mutation, 12.4%.Prior to the first V intake, preventive measures were taken in most patients (hospitalisation 86.1%, hydration 86.7%, antihyperuricemic prophylaxis 72.8%, laboratory assessments 62.7%). The median duration of the ramp-up period was 5.0 weeks (range 1.0 – 23.9), and 72.8% reached the recommended daily dose of 400 mg at the moment of the analysis. In the 62 patients of the evaluable population, the 1-year ORR was 85.5% [95% CI 76.7% - 94.3%]. Considering the median follow-up of patients of 13.1 months, the 1-year estimate for PFS was 80.2% [95% CI 68.8% - 88.6%]. Overall, 81.0% of the 158 patients of the safety population experienced adverse events [AEs, mainly as neutropenia (43.0%) and diarrhoea (23.4%)], 58.2% ≥grade 3 AEs, 45.6% serious AEs (SAEs), and 19.6% V-related SAEs. Three patients experienced 4 fatal V-related AEs (deterioration of the general status, ascites, hepatic failure, and unknown cause at home). Over the ramp-up period, 16 patients (10.1%) experienced tumour lysis syndrome (assessed as serious in 3 patients, 1.9%; leading to treatment discontinuation in 4 patients, 2.5%).
Conclusion
Our first real-world data show that V monotherapy is effective in non-selected pre-treated CLL patients, with similar outcomes as compared to clinical trials. Early safety data are reassuring with few tumour lysis syndromes leading to treatment discontinuation during the ramp-up period. Further results are expected next year.
Keyword(s): BCL2, Chronic lymphocytic leukemia, Targeted therapy