Targeted agents in acute myeloid leukemia in elderly patients

Marina Konopleva, MD, PhD, from the MD Anderson Cancer Centre, Houston, TX, discusses targeted therapies in acute myeloid leukemia (AML) at the International Symposium on Acute Leukemias (ISAL) 2017 in Munich, Germany. She describes trials which specifically target BCL-2 with venetoclax (ABT199), which were developed as a result of pre-clinical work in her lab and the lab of Anthony Letai at the Dana-Farber Cancer Institute. Dr Konopleva summarizes a clinical trial in relapsing refractory AML, which showed a 19% response rate with a single agent, venetoclax (NCT01994837) in heavily pre-treated AML patients. However, Phase I trials currently ongoing in elderly, chemotherapy-unfit AML patients using venetoclax as a frontline therapy together with low dose cytarabine (NCT02287233) or hypomethylating agents (decitabine or azacitadine, NCT02203773) showed a significantly higher response rate of 53% and more than 60% respectively. Dr Konopleva points out that responses were usually seen after one cycle of chemotherapy, and the drugs were well tolerated with an acceptable safety profile. A randomized trial will now be carried out comparing both combinations to standard of care in elderly AML patients unfit for chemotherapy.

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