Abstract / Summary
Background: Acute myeloid leukemia (AML) is the most prevalent type of leukemia, which primarily affects older patients. Because the definition of ‘elderly’ AML varies across the literature, from ≥60 years in some cooperative-group studies to a strict ≥ 75-year threshold in the pivotal VIALE-A trial, we adopt ≥ 60 years as our working definition. Despite recent advancements, the 5-year overall survival (OS) of AML patients is just 30% and declines to 5–10% in patients older than 65 years at diagnosis. The main objective of treatment in older individuals is to achieve complete remission (CR) and maintain a good quality of life. Discussion: Traditionally, intensive chemotherapy (IC) has been used for management of AML since the 1970s. Patients older in age are often not eligible for IC due to factors such as advanced age, comorbidities, and disease characteristics such as high-risk cytogenetics and adverse risk mutations. When considering patients for intensive (and alternative) chemotherapy and allogeneic hematopoietic stem cell transplantation (alloHSCT), we need to consider a standardized fitness assessment tool, which would significantly improve our capacity to individualize treatment strategies and design patient-specific clinical trials. Tools such as performance status, the Ferrara criteria, and comprehensive geriatric assessment (CGA) can help evaluate the baseline comorbidity burden in elderly patients. The discovery of hypomethylating agents (HMAs) like azacitidine and decitabine and BCL-2 inhibitors such as venetoclax has been pivotal in the treatment of elderly AML patients unfit for IC. As our knowledge advances in understanding the pathogenesis of AML, we are learning about new genetic mutations and molecular targets that play an important role in the development of AML. In this revised review, we explicitly separate drugs that are FDA-approved and have been studied specifically in older or unfit AML patients from drugs that are approved but lack dedicated efficacy data in this population and from agents that remain investigational; each tier is summarized in a comparative table of results in all-comers versus results in older/unfit patients and limitations. Advances in reduced-intensity conditioning and GVHD prophylaxis have extended allogeneic transplantation to select fit older patients, while low-dose chemotherapy to manage cell count and supportive care remain vital for non-aggressive pathways. Conclusions: In our review, we have outlined current treatment options for older AML patients, with an emphasis on distinguishing which regimens are supported by dedicated evidence in this population, particularly those unfit for IC.