In May 2019, the FDA approved the combination of venetoclax (Venclexta) and obinutuzumab (Gazyva; VenG) for front-line use in patients with chronic lymphocytic leukemia (CLL). Patients taking this combination receive oral venetoclax for 12 months (ie, 12 28-day treatment cycles) and intravenous (IV) obinutuzumab for 6 months (ie, 6 28-day treatment cycles).
During the ASCO 2020 Virtual Scientific Program, researchers presented long-term results from the CLL14 clinical trial,1 which supported the approval of fixed-duration VenG. Specifically, this trial compared VenG with the combination of fixed-duration chlorambucil and obinutuzumab (CG) in patients with previously untreated CLL who have other medical conditions.
Of the 432 patients who enrolled in CLL14, 216 were randomly assigned to receive VenG and 216 were assigned to receive CG. After a median follow-up of more than 3 years, VenG was shown to be more effective than CG based on measures of progression-free survival. At the 3-year time point, 81.9% of patients on VenG were progression-free compared with 49.5% of patients on CG. This efficacy benefit was seen in all patients, including those with specific high-risk CLL features, such as TP53 mutation or deletion and unmutated IGHV.
Researchers also compared minimal residual disease in patients who were treated with VenG versus those who were treated with CG. Approximately 50% of patients in the VenG arm had no detectable disease compared with 7.4% of those in the CG arm. However, analysis of study data has not shown any differences in overall survival between the 2 treatments.
No new safety concerns were noted in the CLL14 study. However, more patients on VenG therapy were diagnosed with a secondary cancer compared with those on CG therapy (17% vs 10.3%, respectively).
These long-term results from CLL14 suggest that high rates of clinical benefit seen with fixed-duration VenG are maintained after more than 3 years of follow-up. VenG continues to be an important first-line treatment option for patients with CLL, although questions about a potential overall survival advantage remain to be answered.
Reference
- Al-Sawaf O, Zhang C, Tandon M, et al. Fixed-duration venetoclax-obinutuzumab for previously untreated patients with chronic lymphocytic leukemia: follow-up of efficacy and safety results from the multicenter, open-label, randomized, phase III CLL14 trial. J Clin Oncol. 2020;38(15_suppl). Abstract 8027.