Treatment of Unfit Patients With Acute Myeloid Leukemia: A Still Open Clinical Challenge

Older patients with acute myeloid leukemia (AML) more often present with clinically relevant comorbidities. As a consequence, a relevant selection is operated as to inclusion into clinical trials based on intensive induction chemotherapy. However, a lack of validated guidelines results in a considerable heterogeneity in the therapeutic attitude between individual clinicians and clinics. Overall, about 50% of the patients are considered as not eligible for therapy aiming at complete remission (CR) achievement and receive conservative approaches. In order to achieve the best therapeutic results and avoid unnecessary toxicity, it would be of major clinical use to determine which patients will do well with some types of treatment and not other. This is particularly clinical relevant because the > 15% risk of death in the month after the start of treatment is difficult to justify because of median survivals of < 1 year in the patients who do not die early. Therefore, factors other than age significantly influencing survival would be considered and taken into account as soon as diagnosis in the process of therapeutic decision-making. In the recent years promising results have been reported with the use of new drugs, such as clofarabine, cloretazine, hypomethylating agents and vorexolin also in patients with adverse characteristics at diagnosis, but further improvement is urgently needed. In this perspective, AML in the elderly can represent an ideal target patient population to investigate new AML treatment approaches, that may eventually also be of benefit to younger patients with the disease.