UNC Lineberger’s Thomas Alexander, MD, MPH, and colleagues recently published in Cancer Discovery findings from a study that found pairing venetoclax with low-dose navitoclax and chemotherapy had promising efficacy in pediatric and adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia, T-cell acute lymphoblastic leukemia or lymphoblastic lymphoma.
The phase 1 dose escalation study treated 47 patients with venetoclax, a selective B-cell lymphoma 2 (BCL-2) family protein inhibitor, low-dose navitoclax, a BCL-xL/BCL-2 inhibitor, and chemotherapy. In addition to demonstrating treatment efficacy, the study found the combination therapy was largely well-tolerated in patients.
The complete remission rate was 60%, including responses in patients who had previously received hematopoietic cell transplantation or immunotherapy. Thirteen patients (28%) were able to proceed to transplantation or CAR T-cell therapy on study. Neutropenia and thrombocytopenia, an abnormally low level of neutrophils, a type of white blood cells, and platelets, respectively, were the most common adverse events.
“Our study’s findings demonstrate the feasibility of using venetoclax and low-dose navitoclax in combination with standard chemotherapy regimens in patients with relapsed or refractory B-cell and T-cell acute lymphoblastic leukemias and lymphoblastic lymphoma, and we did so while achieving a balance between maximizing efficacy and clinical tolerability,” said Alexander, an assistant professor of pediatrics at UNC School of Medicine.
Looking ahead, Alexander said researchers are working to identify biomarkers to predict who will respond best to this therapy. The trial results are motivating further clinical research incorporating this therapeutic approach in both the relapse and frontline setting.