These studies are interesting, with provocative and compelling findings,” said Timothy Graubert, MD, the Hagler Family Chair in Oncology and Director of the Hematologic Malignancy Program at Massachusetts General Hospital in Boston.
“Bcl-2 proteins regulate cell survival or promote cell death. They can be aberrantly expressed, and the imbalance of these factors can contribute to leukemia initiation and therapeutic resistance. ABT-199 [venetoclax] tips the balance toward cell death,” Dr. Graubert explained.
The study in AML included 40% of patients with secondary AML and 40% who had had three or more prior therapies. “These are bad actors resistant to therapy and high-risk refractory diseases—the worst of the worst,” he stated.
Tumor lysis syndrome has been a concern with this agent. Adjusting the dose downward and monitoring for tumor lysis syndrome seemed to have decreased the risk, he continued. “Thus, this improved safety and tolerability in this study,” Dr. Graubert noted.
The gastrointestinal side effects were manageable and did not lead to treatment discontinuation.
The AML patients with IDH mutations had higher response rates. This unexpected result may turn out to be important, and this observation needs to be studied further, he said. ■
Disclosure: Dr. Graubert reported no potential conflicts of interest.
Venetoclax, formerly known as ABT-199, is moving forward into phase III development in acute myelogenous leukemia (AML) and chronic lymphocytic leukemia (CLL), based on encouraging data from separate phase Ib and II trials presented at the 56th Annual Meeting and Exposition of the American Society...