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FDA Approves Venetoclax for Chronic Lymphocytic Leukemia With 17p Deletion

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On April 11, 2016, the U.S. Food and Drug Administration (FDA) approved venetoclax (Venclexta) for the treatment of patients with chronic lymphocytic leukemia (CLL) with 17p deletion, as detected by an FDA-approved test, who have received at least one prior therapy. Venetoclax is the first FDA-approved treatment that targets the B-cell lymphoma 2 (BCL-2) protein, which supports cancer cell growth and is overexpressed in many patients with CLL.   

“These patients now have a new, targeted therapy that inhibits a protein involved in keeping tumor cells alive,” said Richard Pazdur, MD, Director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “For certain patients with CLL who have not had favorable outcomes with other therapies, [venetoclax] may provide a new option for their specific condition.”

Phase II Trial

The approval was based on the results of a phase II, single-arm trial of venetoclax for the treatment of patients with CLL harboring the 17p deletion who had received at least one prior therapy. The major efficacy outcome measure was overall response rate according to the 2008 Modified IWCLL NCI-WG Guidelines for Tumor Response as evaluated by an independent review committee. Duration of response was an additional outcome measure.  

The trial enrolled 106 patients who had received at least one prior therapy with 17p deletion, as detected by an FDA-approved CLL fluorescence in situ hybridization (FISH) probe kit.  Patients had a median of 2.5 prior treatments (range, 1–10). The overall response rate was 80% (95% confidence interval = 71%–87%) with 8% complete remission (including 2% complete remission with incomplete marrow recovery).  Minimal residual disease was evaluated in peripheral blood and bone marrow for patients who achieved complete response following treatment with venetoclax. Three percent of the patients in the intent-to-treat population achieved a complete remission and were also negative for minimal residual disease in the bone marrow and peripheral blood.  The median time to first response was 0.8 months (range, 0.1–8.1 months).  Median duration of response has not been reached with approximately 12 months median follow-up. The duration of response ranged from 2.9 to more than 19.0 months.

Adverse Reactions

Safety data were evaluated in 240 patients with previously treated CLL who were treated with single-agent venetoclax at a target dose of 400 mg orally daily. The most common (≥ 20%) adverse reactions of any grade were neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, and fatigue. Serious adverse reactions were reported in 44% of patients, and the most common (≥ 2%) serious adverse reactions were pneumonia, febrile neutropenia, pyrexia, autoimmune hemolytic anemia, anemia, and tumor lysis syndrome. 

The recommended dose and schedule for venetoclax for the approved indication is a ramp-up schedule over 5 weeks. Dosing is initiated at 20 mg for 1 week, followed by 1 week at each dose level of 50 mg, 100 mg, and 200 mg, then the recommended daily dose of 400 mg until disease progression or unacceptable toxicity. 

Full prescribing information for venetoclax tablets is available here.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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