AML: New Drugs but New Challenges

Despite the approval of 8 new drugs for acute myeloid leukemia (AML) since 2017, the disease remains challenging, given the significant toxicity associated with available treatments and relatively low cure rates, especially in older adults. Although advantageous for patients, self-congratulatory rejoicing about the new agents would be extremely premature. Questions abound about the need for a specific versus less specific FLT3 inhibitor (eg, midostautin) in the upfront setting and whether a single agent (gilteritnib), albeit better than chemotherapy, is sufficient for relapsed disease. Is the new liposomal formulation of daunorubicin/cytarabine better than ‘3 + 7’ only in secondary AML? Should only those newly diagnosed patients with core binding factor AML routinely receive gemtuzumab ozogamicin? The isocitrate dehydrogenase inhibitors were approved based on non-randomized data; thus, one wonders whether single-agent isocitrate dehydrogenase inhibitor therapy is appropriate for relapsed patients. Glasdegib, an orally available hedgehog inhibitor, is approved in conjunction with low-dose cytarabine in unfit patients but is rarely used in favor of a combination of hypomethylating agents or low-dose cytarabine with venetoclax, which are hopeful newly approved combinations for the older and/or unfit previously untreated. Perhaps venetoclax-based combinations should be more widely used, but the data is currently lacking. Thus, a temperate approach, more clinical research, and a critical analysis of the available data remain important in this “optimistic” new era of AML therapeutics.