For adult patients, “we’ve seen a series of remarkable and well-overdue advances in a space that had not changed much over the prior decades,” hematologist/oncologist Thomas William LeBlanc, MD, associate professor of medicine at Duke University School of Medicine, Durham, North Carolina, said in an interview.
According to the National Cancer Institute, AML will be newly diagnosed in 20,800 patients in 2024, at a median age of 69, and will cause 11,220 deaths. As many as 70% of adult patients will reach complete remission, and 45% of those will live for more than 3 years and potentially be cured. As for children, the Leukemia & Lymphoma Society says the 5-year survival rate from 2012-2018 was 69% for those under 15 years old.
As the American Cancer Society notes, the goal of AML treatment “is to put the leukemia into complete remission (the bone marrow and blood cell counts return to normal), preferably a complete molecular remission (no signs of leukemia in the bone marrow, even using sensitive lab tests), and to keep it that way.”
Chemotherapy Strategies Shift Over Time
In terms of the treatment of adults with AML, “targeted therapies, in addition to the expanding role of venetoclax, has really altered our approach to AML from diagnosis, including after relapse, and later in the disease,” hematologist/oncologist Andrew M. Brunner, MD, of Harvard Medical School and Massachusetts General Hospital, Boston, said in an interview. “The ability to explore these options as monotherapy and in novel combinations has dramatically expanded our treatment options.”
Much depends on the underlying genetic profile of the disease, he said. “There certainly have been gains in patient survival in AML, but those improvements remain fairly heterogeneous and dependent on the underlying genetic profile of the disease. For instance, advances in FLT3- and IDH1/2-mutated AML are a direct result of the improvements in targeted therapies directed at these mutations. Similarly, some molecular and cytogenetic subtypes of AML are particularly responsive to venetoclax-based regimens, and these regimens have been expanded to previously undertreated populations, particularly those over age 60.”
Specifically, Dr. LeBlanc said, the Food and Drug Administration has approved “3 different FLT3 inhibitors, 2 IDH1 inhibitors, 1 IDH2 inhibitor, a BCL-2 inhibitor, a smoothened/hedgehog pathway inhibitor, an oral maintenance chemotherapy/hypomethylating agent (CC-486/oral azacitidine), a CD33-targeting antibody-drug conjugate, and even a novel formulation of two older chemotherapies that improves efficacy in a poor prognosis subgroup (CPX-351/liposomal daunorubicin and cytarabine).”
There’s also been a shift in treatment protocols for patients who were not fit for intensive chemotherapy. In the past, he said, it was standard “to give single-agent hypomethylating chemotherapy with azacitidine or decitabine, or in some contexts, low-dose chemotherapy with cytarabine. Today, many patients who are older and/or more frail are receiving novel therapies either alone or in combination, with greater efficacy and longer duration of response than previously seen with chemotherapy alone.”