Evaluating the long-term effectiveness of fixed-duration treatment with venetoclax plus rituximab in patients with relapsed or refractory chronic lymphocytic leukemia.

This study evaluated the long-term effectiveness of fixed-duration treatment with venetoclax (Venclexta) plus rituximab (Rituxan) in patients with relapsed or refractory (r/r) chronic lymphocytic leukemia (CLL). The data showed that fixed-duration treatment with venetoclax plus rituximab was effective over the long term in these patients.

Chronic lymphocytic leukemia (CLL) is a type of cancer in which the bone marrow makes too many lymphocytes (a type of white blood cell). A high number of patients with CLL experience relapse (worsening of the disease) or refractory (not responsive to the treatment) disease despite treatment. Highly effective targeted therapies have been developed for CLL as it can be challenging to treat.

Targeted therapies are commonly used in the treatment of CLL and improve survival. Venetoclax is a targeted therapy that works by blocking the growth of cancer cells. However, when taken alone only a few patients achieve undetectable minimal residual disease (MRD) response rates and need to be taken indefinitely. MRD is the small number of cancer cells that remain after treatment. The treatment goal is undetectable MRD.

Another, older treatment for CLL involves combining the chemotherapy drug bendamustine (Treanda) and immunotherapy drug rituximab. A previous study showed that combining venetoclax plus rituximab demonstrated high undetectable MRD response rates in blood compared to bendamustine plus rituximab in patients with CLL. However, the long-term effectiveness of fixed-duration treatment with venetoclax plus rituximab in patients with r/r CLL is still unknown.

This study involved 389 patients with r/r CLL. Patients were randomly assigned into 2 groups. Group 1 included 194 patients who received venetoclax plus rituximab for 2 years. Group 2 included 195 patients who received bendamustine plus rituximab for 6 months. The average follow-up time was 59.2 months.

The average survival without cancer worsening was 53.6 months for group 1 versus 17 months for group 2. Patients in group 1 were 81% more likely to survive without cancer worsening than patients in group 2.

After 5 years, 82.1% of the patients in group 1 were alive compared to 62.2% of the patients in group 2. Patients in group 1 were 60% more likely to have a better survival than patients in group 2.

3 years after the end of treatment, patients in group 1 were tested for MRD response rate and divided into 3 subgroups. Group A included 83 patients who had confirmed undetectable MRD. Group B included 23 patients with low MRD response rates. Group C included 12 patients with high MRD response rates. 95.3% of the patients in group A were alive compared to 91.73% of the patients in group B and 72.9% of the patients in group C.

The average time taken from undetectable MRD to MRD conversion was 19 months and 25 months from conversion to progressive disease.

This study concluded that fixed-duration treatment with venetoclax plus rituximab was effective over the long term for the treatment of patients with r/r CLL.

This study was funded by Genentech and AbbVie, the manufacturers of venetoclax.