Dr Daver on the Evolution of Survivorship and Treatment Outcomes in AML

Naval G. Daver, MD, professor, director, Leukemia Research Alliance Program, Department of Leukemia, Division of Cancer Medicine, The University of MD Anderson Cancer Center, discusses the evolution of survivorship in patients with acute myeloid leukemia (AML).

The outlook for AML survivorship has significantly improved over time, Daver begins. A decade ago, options were limited for patients who progressed on standard frontline therapy, such as intensive chemotherapy likeanthracyclines and cytarabine. At that time, no targeted therapies existed; FLT3 inhibitors, IDH inhibitors, and MDM2 inhibitors had not been developed yet, nor had venetoclax (Venclexta) either alone or in combination with hypomethylating agents (HMAs), he reports. Consequently, AML prognosis was dire, with patients having response rates of only 15% to 18% using HMAs alone and even lower rates with low-dose cytarabine, Daver explains. Therefore, approximately 90% of patients had palliative outcomes, according to Daver.

Today, the management of relapsed AML has dramatically changed, Daver continues. The ability to identify molecular targetable mutations, such as FLT3, IDH1, IDH2, NPM1, as well as various fusions and translocations, has become pivotal, he reports. These mutations are found in approximately 55% to 60% of patients, allowing for the use of targeted therapies that yield response rates between 40% to 80%, which is highly encouraging, he emphasizes. Additionally, targeted approaches open the possibility of transitioning patients to allogeneic stem cell transplants, Daver notes.

For those without targetable mutations, venetoclax-based therapies, including combinations with HMAs or intensive chemotherapy, have become viable options, producing response rates of 40% to 70%, he expands. This shift represents a significant change from 10 to 15 years ago, offering new hope for potential cures, according to Daver.

Although cure rates for relapsed and refractory AML still require improvement, ongoing research into immunotherapies—similar to those used in acute lymphoblastic leukemia, multiple myeloma, and large B-cell lymphoma—holds promise, Daver states. Despite challenges, there is growing optimism that survival can be extended and quality of life can be improved for relapsed AML, he concludes.