News >

FDA Grants Venetoclax Full Approval for CLL, Regardless of 17p Deletion

Jason M. Broderick @jasoncology
Published: Friday, Jun 08, 2018

The FDA has granted a standard approval to venetoclax (Venclexta) for the treatment of patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), with or without 17p deletion, following at least 1 prior therapy. The BCL-2 inhibitor is now also approved for use in combination with rituximab (Rituxan) in the same patient population.   

The PFS benefit extended across patients subgroups, including high- and low-risk groups. The 2-year PFS rate among patients with chromosome 17p deletion was 81.5% in the venetoclax arm versus 27.8% with BR (HR, 0.13; 95% CI, 0.05-0.29). For patients without chromosome 17p deletion, the 2-year PFS rate was 85.9% versus 41.0% in favor of the venetoclax arm (HR, 0.19; 95% CI, 0.12-0.32).

Two-year event-free survival also favored the venetoclax group (84.9% vs 34.8%; HR, 0.17; 95% CI, 0.11-0.25). The rate of overall survival (OS) favored the venetoclax arm at 24 months (91.9% vs 86.6%). However, the difference was not statistically significant and neither arm reached median OS (HR, 0.48; 95% CI, 0.25-0.90). 

“Venclexta plus Rituxan provides a new chemotherapy-free option shown to help people live longer without their disease progressing compared to a standard-of-care therapy,” Sandra Horning, MD, chief medical officer and head of Global Product Development, Genentech, which codevelops venetoclax with AbbVie, said in a statement. 

The open-label, international, multicenter phase III MURANO trial included 389 patients with relapsed/refractory CLL who had previously received between 1 and 3 lines of therapy, including at least 1 chemotherapy regimen. Patients were randomly assigned to rituximab plus either venetoclax (n = 194) or bendamustine (n = 195).

Venetoclax was administered at 400 mg orally once daily from cycle 1, day 1 until progression, unacceptable toxicity, or a maximum of 2 years. Treatment was initiated with a 5-week ramp-up schedule with a dose beginning at 20 mg/day for 1 week and then gradually increased to the 400-mg dose. Rituximab was administered at 375 mg/m2 on day 1, cycle 1, followed by 500 mg/m2 on day 1 of cycles 2 through 6. The bendamustine regimen was 70 mg/m2 on days 1 and 2 of cycles 1 through 6. 

In the venetoclax arm, the median age was 64.5 (range 28-83), 27% (46/173) of patients had del(17p), 68% (123/180) of patients had unmutated IGHV, and 25% of patients harbored a TP53 mutation. One hundred eleven patients received 1 prior therapy, 57 patients had 2, 2 patients had 3, and 4 patients had more than 3. Prior treatments including alkylating agent (93%), purine analog (81%), anti-CD20 antibody (78%), and BCR inhibitor (5 patients).

The median age in the BR arm was 66.0 years (range, 22-85), 27% had del(17p), 68% (123/180) of patients had unmutated IGHV, and 28% of patients harbored a mutation. The number of prior therapies included 1 (n = 117), 2 (n = 43), 3 (n = 34), and more than 3 (n = 1). Prior therapies included alkylating agent (95%), purine analog (81%), anti-CD20 antibody (76%), and BCR inhibitor (3 patients).

Grade 3/4 AEs were more common with venetoclax, 82.0% versus 70.2%. Neutropenia was the most common grade 3/4 AE with a higher incidence in the venetoclax arm (57.7% vs. 38.8%). However, incidences of grade 3/4 febrile neutropenia (3.6% vs 9.6%) and grade 3/4 infections or infestations (17.5% vs 21.8%) were lower in the experimental arm.

There were 10 (5.2%) patient deaths in the venetoclax arm, similar to the BR arm (n = 11; 5.9%).

"Venclexta now gives indicated patients a new opportunity to significantly reduce the risk of their disease progressing, compared to a current standard of care. This combination provides previously treated CLL or SLL patients with a chemotherapy-free, fixed duration treatment allowing patients the ability to stop treatment after approximately two years,” Michael Severino, MD, executive vice president, research and development, and chief scientific officer, AbbVie, said in a statement. 
Seymour JF, Kippes TJ, Eichhorst B, et al. Venetoclax–rituximab in relapsed or refractory chronic lymphocytic leukemia [published online March 22, 2018]. N Engl J Med. 2018; 378:1107-1120. doi: 10.1056/NEJMoa1713976.

 



... to read the full story
To Read the Full Story

View Conference Coverage
Online CME Activities
TitleExpiration DateCME Credits
Community Practice Connections™: 22nd Annual International Congress on Hematologic Malignancies®: Focus on Leukemias, Lymphomas and MyelomaMay 30, 20192.0
Online Medical Crossfire®: 5th Annual Miami Lung Cancer ConferenceMay 30, 20196.5
Publication Bottom Border
Border Publication
x