Patients with chronic lymphocytic leukaemia (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 over-expressed in CLL, leading to the accumulation of leukaemia cells.

In a previous Phase I study, venetoclax demonstrated a 77 percent overall response rate for patients with relapsed or treatment-resistant CLL.

A pivotal 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.

Patients remained on daily 400 mg 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.

The overall response rate was 79.4 percent.

Of all responders, 84.7 percent maintained their response at 12 months.

More than 20 percent of responders had undetectable leukaemia cells after therapy.

More than 10 percent of patients achieved “deep responses” (i.e., no detectable disease or only minimal nodules remaining in the bone marrow), a predictor of long-term remission which has not been previously reported in this population.

Toxicity was acceptable in this extremely high-risk patient population.

Among 11 deaths, seven were due to progressive disease, and four due to adverse events.

Results suggest that venetoclax is a promising option for this very difficult-to-treat CLL patient population characterised by 17p deletion.

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Source: ASH