June 08, 2018—Today, the U.S. Food and Drug Administration (FDA) approved the use of venetoclax for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have received at least one prior therapy, regardless of 17p deletion status. The BCL-2 inhibitor had previously been granted accelerated approval in April 2016.
Full approval was based on data from the phase III MURANO (NCT02005471), in which 389 patients with CLL were randomized (1:1) to receive venetoclax plus rituximab or bendamustine in combination with rituximab. All patients had received at least one prior line of therapy.
For patients receiving venetoclax, the overall response rate (ORR) was 92%, versus 72% for the control arm. Further, with a median follow-up of 23.8 months the median progression-free survival (PFS) had not yet been reached in the venetoclax arm, compared with 18.1 months in the control arm.
In results published in the New England Journal of Medicine, investigators reported a 2-year PFS rate of 84.9% and 36.3%, for the venetoclax and control arms respectively. This benefit to PFS was observed across all clinical and biologic subgroups, including high- and low-risk patients with or without chromosome 17p deletions.
The 2-year PFS rates among patients with chromosome 17p deletions were 81.5% in the venetoclax group versus 27.8% in the control group; among those without chromosome 17p deletions, the 2-year PFS rates were 85.9% and 41.0%, respectively.
Grade 3/4 adverse events (AEs) were more common in patients receiving venetoclax (82.0%) than patients on the control arm (70.2%). The rate of grade 3/4 neutropenia was higher in the venetoclax group (57.7%) than in the control group (38.8%), but the rates of grade 3/4 febrile neutropenia (3.6% vs 9.6%) and infections (17.5% vs 21.8%) were lower with venetoclax arm than the control arm.
Due to rapid reduction in tumor volume, venetoclax contains a box warning for tumor lysis syndrome (TLS). In the MURANO trial the rate of grade 3/4 TLS in the venetoclax group was 3.1%.
Prescribing information for venetoclax can be found here.
Jonathan A. Bell
Published Online: Friday, June 08, 2018