A Phase II clinical trial at The University of Texas MD Anderson Cancer Center has demonstrated promising results using a novel triplet therapy for patients with advanced-phase chronic myeloid leukemia (CML) and Philadelphia chromosome-positive acute myeloid leukemia (AML). The study, published in The Lancet Haematology, found that 80% of patients treated with a combination of decitabine, venetoclax, and ponatinib achieved bone marrow remission.
This research marks a significant advancement for patients with advanced-phase CML, who typically face poor outcomes due to limited standard-of-care treatment options. The trial enrolled 20 patients, including those with myeloid blast-phase CML (14 patients), accelerated-phase CML (4 patients), and Philadelphia chromosome-positive AML (2 patients).
Key Findings
The study revealed that 50% of patients achieved either complete remission or complete remission with incomplete hematological recovery. An additional 30% reached a morphologic leukemia-free state. Notably, the triplet therapy was effective even in patients who had previously undergone multiple treatments and those with high-risk cytogenetic or molecular characteristics.
According to Nicholas Short, M.D., principal investigator and associate professor of Leukemia, "Over the last decade, there have been very few studies that evaluated a regimen to treat this rare disease and identify a potential standard-of-care treatment. It is important that we get these patients into a state of marrow remission as this will allow them to be considered for a stem cell transplant. We were able to achieve this response in 80% of patients on this trial."
Rationale Behind the Therapy
The triplet combination leverages the synergy between venetoclax, a BCL-2 inhibitor, and ponatinib, a BCR::ABL1 tyrosine kinase inhibitor. "For this trial, we were able to build on previous preclinical and clinical research conducted at MD Anderson, which identified synergy between the BCL-2 inhibitor, venetoclax and the BCR::ABL1 tyrosine kinase inhibitor, ponatinib," Short explained. "This knowledge led us to consider this novel treatment regimen for this aggressive disease."
Safety Profile
The researchers reported that the observed side effects were consistent with those previously associated with the individual drugs. Common adverse events included neutropenia, rash, and nausea.
Ongoing Research
The clinical trial is still ongoing, with continued enrollment of additional patients. Furthermore, MD Anderson researchers are pursuing additional studies to explore new combinations of targeted therapies for advanced-phase CML.
Funding
The trial received funding from Takeda Oncology, the National Institutes of Health, and the National Cancer Institute Cancer Center Support Grant.
