ASH 2015: Venetoclax Shows Promise for Ultra–High-Risk Chronic Lymphocytic Leukemia With 17p Deletion
In a study to be presented at the 57th American Society of Hematology (ASH) Annual Meeting by Stilgenbauer et al, monotherapy with the investigational agent venetoclax (ABT-199/GDC-0199) induced deep remissions—including complete remission and undetectable minimal residual disease—in ultra–high-risk relapsed/refractory chronic lymphocytic leukemia (CLL) with 17p deletion (Abstract LBA-6).
Patients with CLL harboring 17p deletion have a particularly poor prognosis and limited treatment options. Venetoclax is an oral, targeted drug that inhibits BCL-2, a protein that regulates natural cell death. BCL-2 is overexpressed in CLL, leading to the accumulation of leukemia cells. In a previous phase I study, venetoclax demonstrated a 77% overall response rate for patients with relapsed or treatment-resistant CLL.
Study Details
A phase II trial was conducted to assess efficacy in CLL patients with 17p deletion. A total of 107 patients with relapsed or treatment-resistant disease took venetoclax once daily with a weekly dose ramp-up schedule (20, 50, 100, 200, 400 mg) over a period of 5 weeks. Patients remained on daily 400-mg venetoclax until disease progression or discontinuation for another reason.
The primary endpoint was overall response rate as assessed by an independent committee. Efficacy was examined once patients had completed 36 weeks of venetoclax, experienced disease progression, or discontinued the trial.
Study Findings
The overall response rate was 79.4% (95% confidence interval = 70.5%–86.6%). Of all responders, 84.7% maintained their response at 12 months.
More than 20% of responders had undetectable leukemia cells after therapy. More than 10% of patients achieved “deep responses” (ie, no detectable disease or only minimal nodules remaining in the bone marrow), a predictor of long-term remission that has not been previously reported in this population.
Toxicity was acceptable in this extremely high-risk patient population. Among 11 deaths, 7 were due to progressive disease, and 4 due to adverse events.
Results suggest that venetoclax is a promising option for this very difficult-to-treat CLL patient population characterized by 17p deletion. The investigators noted that “such depths of response have not been previously reported for this population.”
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