Study Confirms Venetoclax Activity in CLL

May 18, 2016

A phase II study of the BCL2 inhibitor venetoclax has shown that a large majority of patients with relapsed or refractory chronic lymphocytic leukemia responded to treatment with the drug.

A phase II study of the BCL2 inhibitor venetoclax has shown that a large majority of patients with relapsed or refractory chronic lymphocytic leukemia responded to treatment with the drug. The drug received US Food and Drug Administration approval last month.

“By combining a manageable safety profile with deep responses, venetoclax is a good available option to treat patients with relapsed and refractory del(17p) chronic lymphocytic leukemia,” wrote authors led by Stephan Stilgenbauer, MD, Ulm University, Germany.

According to the study, published in Lancet Oncology, patients with relapsed or refractory chronic lymphocytic leukemia with the 17p deletion have poor response to treatment with standard chemo-immunotherapy. A phase I study of venetoclax showed that 77% of patients with relapsed or refractory chronic lymphocytic leukemia responded to the drug.

In this phase II study, Stilgenbauer and colleagues enrolled 107 patients aged 18 or older with chronic lymphocytic leukemia and a 17p deletion from 31 centers. Patients were given once daily venetoclax with a weekly dose increase schedule from 20 mg to 400 mg over 4 to 5 weeks. After that time, patients were given a continuous dose of 400 mg until disease progression.

After a median follow-up of about 1 year, 79.4% of patients in the study had a response (95% CI, 70.5–86.6). According to the researchers, this response was similar to that of “the broader relapsed and refractory chronic lymphocytic leukemia population in the first-in-human venetoclax study, which strongly suggests that the mechanism by which venetoclax kills chronic lymphocytic leukemia cells might overcome dysfunctional p53.”

The median time to response was 0.8 months, which demonstrates that, “the rapid reduction of chronic lymphocytic leukemia cells poses a risk for tumor lysis syndrome when starting venetoclax.”

The researchers found that response to venetoclax was not affected by a patient being refractory to a prior treatment, the proportion of chronic lymphocytic leukemia cells with 17p deletion, the presence of TP53 mutation, or other characteristics associated with poor outcomes.

The most commonly occurring grade 3/4 adverse events were neutropenia (40%), infection (20%), anemia (18%), and thrombocytopenia (15%). In addition, 55% of patients had a serious adverse event.

“Our results show that BCL2 inhibition with venetoclax might offer an opportunity to effectively treat del(17p) chronic lymphocytic leukemia in addition to other available agents, such as ibrutinib and idelalisib, which have already led to a dramatic advancement in management of these patients,” the researchers wrote.