Researchers have found that 80% of patients with previously treated or relapsed/refractory advanced-phase chronic myeloid leukemia (CML)—including both accelerated or myeloid blast phases of the disease—or Philadelphia chromosome–positive acute myeloid leukemia (AML) may have achieved a bone marrow remission following treatment with a novel triplet combination, according to a study published by Short et al in The Lancet Haematology. The findings represented a significant step forward for patients with advanced-phase CML.
Background
Patients with advanced-phase CML typically have poor outcomes. Because there are currently limited data on a standard-of-care approach to treat the disease, there is a critical need for studies investigating additional therapeutic options in this patient population.
“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,” emphasized lead study author Nicholas Short, MD, Associate Professor of Leukemia at The University of Texas MD Anderson Cancer Center. “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,” he continued.
Study Methods and Results
In the phase II clinical trial, the researchers assigned 14 patients with myeloid blast–phase CML, 4 patients with accelerated-phase CML, and 2 patients with Philadelphia chromosome–positive AML to receive the triplet combination of decitabine, venetoclax, and ponatinib.
Overall, 50% of the patients achieved a complete remission or complete remission with incomplete hematologic recovery, and an additional 30% of the patients achieved a morphologic leukemia-free state. Further, responses were observed in patients who had received multiple lines of prior therapies and in those with high-risk cytogenetic or molecular features.
The researchers observed expected side effects, which were consistent with previous studies exploring the drugs. Common side effects included neutropenia, rash, and nausea.
Conclusions
“We were able to achieve this response in 80% of patients on this trial. [W]e were able to build on previous preclinical and clinical research conducted at MD Anderson, which identified synergy between the BCL2 inhibitor venetoclax and the BCR::ABL1 tyrosine kinase inhibitor ponatinib,” Dr. Short underscored. “This knowledge led us to consider this novel treatment regimen for this aggressive disease,” he revealed.
The researchers noted that the trial is ongoing and enrolling additional patients. They are also conducting further studies building on the approach of adding targeted therapies into new treatment combinations in patients with advanced-phase CML.
Disclosure: The research in this study was funded by Takeda Oncology, the National Institutes of Health, and the National Cancer Institute Cancer Center Support Grant. For full disclosures of the study authors, visit thelancet.com.
