Ibrutinib and venetoclax treatment for patients with relapsed or refractory chronic lymphocytic leukemia according to minimal residual disease status.

This study investigated the effectiveness and safety of time-limited treatment with ibrutinib (Imbruvica) plus venetoclax (Venclexta) for patients with relapsed or refractory (r/r) chronic lymphocytic leukemia (CLL) by using minimal residual disease (MRD) guidance. The data showed that time-limited treatment with ibrutinib plus venetoclax was safe and effective for these patients.

CLL is a type of cancer that affects the blood and bone marrow. 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.

Ibrutinib and venetoclax are targeted therapies that work by blocking the growth of cancer cells. Both targeted therapies are commonly used in treating CLL and have shown good effectiveness. However, only a few patients achieve undetectable minimal residual disease (MRD) response rates when taken alone. Therefore these medications need to be taken indefinitely. MRD is the small number of cancer cells that remain after treatment.

The treatment goal is undetectable MRD. Targeted time-limited treatment options are needed for patients with r/r CLL. It is important to evaluate whether giving both ibrutinib and venetoclax to patients with r/r CLL and using MRD guidance on when to stop treatment is safe and effective.  

This study involved 225 patients with r/r CLL who received 15 cycles of combined ibrutinib plus venetoclax. Patients were tested for MRD response rate and divided into 2 groups. Group 1 included 72 patients who had confirmed undetectable MRD and were randomly assigned to ibrutinib maintenance treatment (24) or stopped treatment (48). Group 2 included 153 patients who did not have confirmed undetectable MRD and continued treatment with ibrutinib. alone The average follow-up time was 34.4 months.

After 12 months of observation, 98% of the patients in group 1 who stopped treatment were alive without cancer worsening. For patients in group 1 who continued ibrutinib maintenance, 96% of these patients were alive without cancer worsening after 12 months.

In group 2, 97% of patients were alive after 12 months of observation. 

It was estimated that after 27 months (15 cycles of ibrutinib plus venetoclax and 12 months of observation), 94% of all patients were alive. 

The most common side effects were infections, low white blood cell counts, and gastrointestinal-related side effects. Serious side effects were reported in 33% of the patients in group 1 who received ibrutinib, 8% of the patients in group 1 who stopped treatment, and 40% of the patients in group 2.

This study concluded that time-limited treatment with ibrutinib plus venetoclax was safe and effective for the treatment of patients with r/r CLL.

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