Combining ibrutinib and venetoclax for treatment of chronic lymphocytic leukemia

This study aimed to investigate if combining ibrutinib and venetoclax would enable the eradication of chronic lymphocytic leukemia and allow therapy to end.  

This study concluded that this combination was safe and effective in these patients and that therapy cessation was achieved for some patients.  

Ibrutinib (Imbruvica) is a targeted therapy that works to stop the reproduction of cancer cells. Venetoclax (Venclexta) is also a targeted therapy and it encourages cancer cell death. Both targeted therapies are commonly used in the treatment of chronic lymphocytic leukemia (CLL) and improve survival. When taken alone, however, they rarely lead to the total eradication of minimal residual disease (MRD) and need to be taken indefinitely. MRD is the small number of cancer cells that remain after treatment.  

It was unknown if combining ibrutinib and venetoclax would enable the eradication of CLL and allow therapy to be ended. 

This study involved 53 patients with relapsed or unresponsive CLL. Patients received a combination treatment of ibrutinib and venetoclax. Patients were followed for 12 months. The outcome measured was the eradication of MRD. Other outcomes were safety, progression-free survival (PFS – survival without the disease getting worse) and overall survival (OS).  

MRD negativity (less than one CLL cell in 10,000 blood cells) was found in the blood of 53% of patients. MRD negativity was found in the marrow of 36% of patients. 89% of patients responded to treatment and 51% achieved a complete remission (all signs of cancer gone).   

After 21.1 months, one patient's cancer progressed and all patients were alive.  

One case of tumor lysis syndrome (metabolic and electrolyte abnormalities) was experienced. Other mild side effects were neutropenia (low level of white blood cells) and gastrointestinal events. 

This study concluded that the combination of ibrutinib and venetoclax was safe and effective in CLL patients and that therapy cessation was achieved for some. 

This study had a limited number of patients. Further studies are needed.  

This study was partly funded by Janssen Pharmaceuticals and Pharmacyclics, the manufacturers of ibrutinib.