Dr. Donnellan on Combinations Under Investigation in Acute Leukemia

William B. Donnellan, MD
Published: Wednesday, Mar 21, 2018



William B. Donnellan, MD, investigator, Hematologic Malignancies, Sarah Cannon Research Institute, Tennessee Oncology, discusses combinations under investigation in acute leukemia.

In 2017, there were 7 new drug approvals in acute leukemia. Donnellan says that the next big question is whether this new crop of agents will demonstrate added benefit when combined. Specifically, Donnellan says that investigators need to determine whether there is an added benefit of combining CPX-351 with a FLT3 inhibitor, such as midostaurin (Rydapt), or with some of the second-generation FLT3 inhibitors. Or, whether combining enasidenib, the IDH2 inhibitor, with other small molecules in patients with secondary acute myeloid leukemia (AML) who also have a FLT3 mutation adds benefit.

Combinations are something to look forward to, says Donnellan. One of the big stories out of the 2017 ASH Annual Meeting was venetoclax (Venclexta), which showed very high response rates when used in combination with a hypomethylating agent in patients with newly diagnosed AML.

A phase III study is set to launch comparing azacitidine either in combination with venetoclax or placebo. That trial could potentially change the treatment paradigm for elderly patients who are not fit for induction, Donnellan says.


William B. Donnellan, MD, investigator, Hematologic Malignancies, Sarah Cannon Research Institute, Tennessee Oncology, discusses combinations under investigation in acute leukemia.

In 2017, there were 7 new drug approvals in acute leukemia. Donnellan says that the next big question is whether this new crop of agents will demonstrate added benefit when combined. Specifically, Donnellan says that investigators need to determine whether there is an added benefit of combining CPX-351 with a FLT3 inhibitor, such as midostaurin (Rydapt), or with some of the second-generation FLT3 inhibitors. Or, whether combining enasidenib, the IDH2 inhibitor, with other small molecules in patients with secondary acute myeloid leukemia (AML) who also have a FLT3 mutation adds benefit.

Combinations are something to look forward to, says Donnellan. One of the big stories out of the 2017 ASH Annual Meeting was venetoclax (Venclexta), which showed very high response rates when used in combination with a hypomethylating agent in patients with newly diagnosed AML.

A phase III study is set to launch comparing azacitidine either in combination with venetoclax or placebo. That trial could potentially change the treatment paradigm for elderly patients who are not fit for induction, Donnellan says.



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