A review of venetoclax for previously treated CLL

This study reviewed evidence on venetoclax (Venclexta) for previously treated chronic lymphocytic leukemia (CLL).

Targeted therapy is the standard treatment of CLL. This includes the BCL2 inhibitor therapy venetoclax. BCL2 inhibitor therapy blocks a protein called BCL2 involved in leukemia cell growth. Venetoclax has recently been approved for patients with CLL who have relapsed (return of the disease) or are no longer responding to standard therapy (refractory disease).

The first study to examine venetoclax reported a response rate of 79% in CLL patients with relapsed or refractory CLL. The observed anti-cancer effect occurred fast. A decrease in CLL cells in the blood was detected within 6 to 24 hours of the first dose. The size and extent of the tumor reduced significantly. The depth of the response increased over time, especially in the bone marrow and lymph nodes. Doses ranging from 150 to 1,200 mg per day resulted in complete remissions in 20% of patients. Factors such as genetic abnormalities and older age (typically making CLL more difficult to treat) were not found to affect treatment outcomes.

A second study examined the effects of venetoclax in 107 patients with relapsed CLL. 79% of patients showed treatment response. The overall response rate was 72% at 12 months. This was similar for patients with refractory disease and for patients with and without genetic abnormalities (including deletion (17p) or TP53 mutation). Average time to the first detectable response was 0.8 months. Average time to complete response was 8 months.

Venetoclax has been suggested to make cancer cells more sensitive to other drugs. Early results are promising on the combination of venetoclax with the monoclonal antibody therapy rituximab (Rituximab). However, more studies are needed.

Venetoclax is generally well tolerated. Some patients report mild stomach-related side effects, such as nausea and loose bowel movements, especially early in the course of treatment. Low red and white blood cell counts are a common treatment-related side effect.

The most serious possible complication is tumor lysis syndrome. This is when a large number of cancer cells are killed at once and their byproducts enter the bloodstream. If left untreated, it can lead to acute kidney failure, heart rate problems, neurological complications, and seizures. Venetoclax should therefore be started at a low dose (20 mg per day for the first week) with a gradually increasing dose to the recommended 400 mg per day. All patients should be monitored for tumor lysis syndrome when treatment is started. 

Authors concluded that venetoclax is an effective treatment for difficult-to-treat CLL such as relapsed or refractory disease and the presence of genetic abnormalities.