In a nutshell
This study examined venetoclax (Venclexta) for patients with chronic lymphocytic leukemia (CLL) previously treated with ibrutinib (Imbruvica). Researchers reported good disease control and a low rate of side effects venetoclax after ibrutinib.
Targeted therapy is the standard treatment of CLL. This includes the Bruton tyrosine kinase inhibitor ibrutinib. Ibrutinib blocks a signal that keeps the CLL cell alive. Many patients achieve complete remission with ibrutinib therapy. However, some patients stop responding to ibrutinib (refractory) or relapse after therapy. These patients can be difficult to treat. Relapse is observed more frequently in high-risk patients such as those with certain genetic abnormalities due to CLL.
Venetoclax has recently been approved for relapsed or refractory CLL. It may be particularly suited for patients previously treated with ibrutinib.
Methods & findings
91 CLL patients previously treated with ibrutinib were included in this study. 55% of patients discontinued ibrutinib due to disease progression. 33% discontinued due to side effects. Other reasons included achievement of maximal clinical benefit (7%) and the end of a defined treatment course (3%). All patients were then treated with venetoclax. The starting dose was 20 mg per day that was increased to 400 mg over 5 weeks. Treatment outcomes were followed up for an average of 14 months.
51% of patients are currently still receiving venetoclax. 65% of patients showed an overall response to treatment. The average time to this response was 2.5 months. 56% of patients showed a partial response to treatment. 9% of patients achieved a complete response. Response rates were similar for patients with and those without genetic abnormalities.
26 patients progressed during venetoclax therapy. 7 patients died due to disease progression. The average time to disease progression was 24.7 months. 80% of patients were progression-free at 12 months. The estimated overall survival rate (proportion who have not died from any cause since treatment) was 91% for 12 months. The most common serious side effects were related to low white and red blood cells counts.
The bottom line
This study concluded that venetoclax was associated with a high overall response rate in patients progressing after, or no longer responding to, ibrutinib.
The fine print
This is an interim analysis of an ongoing study. Larger studies over a longer period of time may give a better indication of the effects of venetoclax after ibrutinib.
Published By :
The Lancet. Oncology
Dec 12, 2017