Evolving Therapeutic Approaches for Older Patients with Acute Myeloid Leukemia 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.

Keywords: acute myeloid leukemia; elderly; fitness; precision medicine; targeted therapy.

Figure 1

Selected cellular pathways targeted by new AML drugs.

Figure 2

Treatment algorithm ^§ of older AML patients that we follow in 2021. Abbreviations: Allo-HCT, allogeneic hematopoietic cell transplantation; ADV, adverse; BSC, best supportive care; FAV, favorable; HMA, hypomethylating agents; IC, intensive chemotherapy; INT, intermediate; LDAC, low-dose cytarabine; VEN, venetoclax. ^§ The discussion regarding the type of consolidation or maintenance therapy is not included. ° Age cut-offs are somewhat arbitrary, and they are used to simplify the algorithm. They are never absolute. * In cases of moderate comorbidities, IC is usually preferred in this age group. In cases of significant cardiac comorbidity, a regimen without anthracycline can be considered (e.g., FLAG). ^# Intensive chemotherapy according to the disease profile (i.e., 7+3 and GO, 7+3 and midostaurin, CPX-351, FLAG-ida, 7+3). ^ƪ Above 70 years of age, dose reductions are usually considered, such as 2+5 with midostaurin and a 4-day regimen of FLAI. CPX-351 is administered at full dose when employed. ^ Especially when features predicting a good chance of response are present, such as non-proliferative disease.