Venetoclax-Based Combination Therapies Revolutionize Paradigm for Elderly AML

Naval G. Daver, MD, associate professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, discusses the activity seen with venetoclax (Venclexta)-based therapies in elderly patients with acute myeloid leukemia (AML).

Both hypomethylating agents (HMAs) azacitidine (Vidaza) or decitabine (Dacogen) have been investigated in phase II clinical trials in combination with venetoclax. Venetoclax was approved by the FDA for use in combination with each of these agents in this setting. In elderly patients with AML, these combinations demonstrate response rates around 70% to 75% with a median overall survival of 18 to 20 months. Daver says this is about 2 to 3 times higher than what has been seen with either single-agent HMA.

After 3-year follow-up, 45% of patients are still alive compared to historical data of 10% to 15% for this elderly population. This is a major improvement that has revolutionized the treatment paradigm for these patients, says Daver. Low-dose cytarabine plus venetoclax has also shown similar promise, although the response rates have been a bit lower than the HMA/venetoclax combinations. However, the response rates are still 4 to 5 times higher in combination with venetoclax compared to cytarabine alone.

Both the cytarabine and HMA combinations with venetoclax are being used in the frontline; because the regimens are not mutation-agnostic, patients with FLT3, IDH, and other mutations can receive treatment as well. This is important to the community, Daver concludes, because physicians do not need to wait for mutational data to begin treatment if a patient is not a candidate for chemotherapy or is elderly.