Evolving Therapeutic Approaches for Older Patients with Acute Myeloid Leukemia in 2021

SIMPLE SUMMARY: The better understanding of disease biology, the availability of new effective drugs and the increased awareness of patients’ heterogeneity in terms of fitness and personal expectations has made the current treatment paradigm of AML in the elderly very challenging. Here, we discuss the evolving criteria used to define eligibility for induction chemotherapy and transplantation, the introduction of new agents in the treatment of patients with very different clinical conditions, the implications of precision medicine and the importance of quality of life and supportive care, proposing a simplified algorithm that we follow in 2021. ABSTRACT: Acute myeloid leukemia (AML) in older patients is characterized by unfavorable prognosis due to adverse disease features and a high rate of treatment-related complications. Classical therapeutic options range from intensive chemotherapy in fit patients, potentially followed by allogeneic hematopoietic cell transplantation (allo-HCT), to hypomethylating agents or palliative care alone for unfit/frail ones. In the era of precision medicine, the treatment paradigm of AML is rapidly changing. On the one hand, a plethora of new targeted drugs with good tolerability profiles are becoming available, offering the possibility to achieve a prolonged remission to many patients not otherwise eligible for more intensive therapies. On the other hand, better tools to assess patients’ fitness and improvements in the selection and management of those undergoing allo-HCT will hopefully reduce treatment-related mortality and complications. Importantly, a detailed genetic characterization of AML has become of paramount importance to choose the best therapeutic option in both intensively treated and unfit patients. Finally, improving supportive care and quality of life is of major importance in this age group, especially for the minority of patients that are still candidates for palliative care because of very poor clinical conditions or unwillingness to receive active treatments. In the present review, we discuss the evolving approaches in the treatment of older AML patients, which is becoming increasingly challenging following the advent of new effective drugs for a very heterogeneous and complex population.