Combining venetoclax and navitoclax with chemotherapy in patients with relapsed/refractory acute lymphoblastic leukemia and lymphoblastic lymphoma

This study aimed to investigate the safety and effectiveness of venetoclax (Venclexta) and low-dose navitoclax (ABT-263) in combination with chemotherapy in patients with relapsed/refractory (r/r) acute lymphoblastic leukemia (ALL). 

This study concluded that this treatment option was well tolerated and showed promissing effectiveness in these patients. 

Venetoclax is a type of targeted therapy known as a BCL2 inhibitor. It is approved for the treatment of certain types of leukemia. Navitoclax is also a BCL2 inhibitor. It is an experimental treatment and can be dose-limited due to the side effect of thrombocytopenia (low level of platelets). 

It was unknown if venetoclax and low-dose navitoclax could be combined with chemotherapy to provide a safe and effective treatment for patients with r/r ALL.

This study involved 47 patients with r/r ALL or lymphoblastic lymphoma (LL). Patients had an average of 4 prior treatments. All patients were treated with navitoclax, venetoclax, and chemotherapy. 

The complete remission (CR) rate was 60%. The CR rate was 75% in pediatric patients. Undetected minimal residual disease MRD was seen in 34% of all patients and 57% of pediatric patients. MRD is a small number of cancer cells left after treatment that can lead to relapse. 28% of patients proceeded to transplantation or CAR T-cell therapy. 

The most common side effects were low levels of white blood cells with fever, diarrhea, nausea (46.8% each), low levels of potassium (44.7%), and abdominal pain (42.6%). 78.7% of patients experienced serious side effects including low white blood cells with fever and generalized infection.

This study concluded that venetoclax and navitoclax with chemotherapy combination was well tolerated and had a promising effectiveness in patients with r/r ALL.  

This study had a very small number of participants. Further, larger studies are needed to evaluate this combination in patients with r/r ALL.