Dr Jeffrey Lancet Discusses Best Practices for Treating AML

Jeffrey E. Lancet, MD, chair of the Department of Malignant Hematology at Moffitt Cancer Center in Tampa, Florida, gave his insight on the treatment of acute myeloid leukemia (AML) across patient groups.

Transcript

What are the current best practices for treating patients with AML?

There are several different approaches to treating patients with AML depending on a variety of factors, including a patient's age, the patient's level of physical and functional fitness, and, perhaps most importantly, the underlying biology of the disease as reflected in the genetic profile of the leukemia. Best practices really depend on those factors.

The best practice for a young patient with a favorable genetic subtype of AML is typically an aggressive induction chemotherapy course with daunorubicin plus cytarabine and possibly with the addition of a third drug such as mylotarg or gemtuzumab, or, for example, a FLT3 inhibitor midostaurin, would be standard of care for patients with mutations of FLT3 who are felt to be younger and more fit. And with a FLT3 mutation, that generally confers at least initial chemosensitivity.

When you get into the realm of older, less fit, maybe frail patients with AML many times that has evolved from prior hematologic illness such as MDS [myelodysplastic syndrome], the standard of care, the best practice would typically involve the use of an azanucleoside drug such as 5-azacytidine, in combination with a BCL2 inhibitor, known as venetoclax. And that combination has really become entrenched as a standard of care for older, less fit patients with perhaps other comorbidities that would probably not benefit from a more intensive induction in terms of toxicity and mortality risks.

I think best practices are starting to incorporate more targeted therapies based upon the molecular genetic profile of the disease at baseline—I talked just a moment ago about the use of midostaurin, a FLT3 inhibitor, being added to induction chemotherapy. We also have targeted drugs known as IDH inhibitors that are relevant for patients with IDH1 or IDH2 mutations that can be combined with azanucleosides—but not yet with venetoclax, because the triplet combination has not yet been fully established as a standard of care—but a doublet of azanucleoside plus an IDH inhibitor is very appropriate best practice therapy for older patients who carry the IDH mutation.

There are other mutations on the landscape that are becoming more targetable and that are being tested for therapy in earlier-phase studies that may eventually become incorporated into the more standard regimens and perhaps even replace some of the other current drugs in those regimens if the activity level is high.

Best practices can also include allogeneic, bone marrow, or stem-cell transplant for more fit patients even up to age 75. Patients with good underlying health and functional status and lack of comorbidities are often good candidates for stem-cell transplant, especially if they have nonfavorable leukemia—in other words, genetically intermediate or adverse risk when we know that there's a high chance of a future relapse. Those patients are often suitable candidates for allogeneic transplant, which has realistically the only potentially curative potential in these higher-risk patients. So, there's a variety of best practices that we can consider, but they're definitely reliant upon a variety of factors that we need to consider before we commit to any one treatment.