Effectiveness and Safety of Therapeutic Regimens for Elderly Patients With Acute Myeloid Leukemia: A Systematic Literature Review

Abstract

Acute myeloid leukemia (AML) is the second most common leukemia among adults. Although the median age at diagnosis is 67 years, with approximately one third of patients aged 75 years or older, limited treatment options exist for the elderly, who have 5-year survival rates of only 5%. A systematic review was conducted to examine effectiveness and safety outcomes of treatment regimens in elderly (≥60 years old) patients with AML. Published literature on the topic was scant, and the review included only 22 articles examining outcomes. Twelve studies examined treatment-specific outcomes; most of these examined azacitidine or intensive chemotherapy (IC). An international randomized controlled trial found that azacitidine significantly improved overall survival relative to conventional regimens including IC and low-dose cytarabine in patients aged > 65 years. Similar results in favor of azacitidine were demonstrated in 2 other studies. IC was generally associated with longer survival versus lower-intensity therapy or best supportive care. Findings suggest that azacitidine is a viable option for elderly AML patients who are ineligible for IC, and emerging agents used in combination with azacitidine could have a major impact in this difficult-to-treat population.

Current Therapeutic Results and Treatment Options for Older Patients with Relapsed Acute Myeloid Leukemia

“…New treatment options, including venetoclax in combination with HMAs or LDARAC [7] and glasdegib in combination with LDARAC [8], have recently been approved by the Food and Drug Administration (FDA) for the treatment of newly diagnosed patients aged over 75 years and/or ineligible for intensive induction, where the treatments are expected to improve the clinical outcome. Following administration of conventional induction ICT, complete remission (CR) rates ranging from 40% to 70% are currently reported in untreated patients, depending on cytogenetics and molecular characteristics at diagnosis [9,10]. CR rate, including CR with incomplete hematological recovery (CRi), drops to 20%–25% after treatment with HMA and to less than 15% with LDARAC [11,12,13,14].…”

Pan-cancer analysis reveals unique molecular patterns associated with age

“…Given the extensive epigenomic aberrations seen in young patients, it is possible that these neoantigens may be epigenetically silenced. This, in turn, would lead to poor prognosis even though the patients are enriched for immune pathways, potentially explaining the increased sensitivity of epigenetic drugs in younger patients (Bell et al, 2018). While the datasets used for this analysis did not have a substantial amount of triple negative cases, future population-based studies could test this hypothesis.…”

Patient-Centered Insights on Treatment Decision Making and Living with Acute Myeloid Leukemia and Other Hematologic Cancers

“…Acute myeloid leukemia (AML) is one of the most prevalent types of blood malignancies, although overall it is a rare orphan malignancy [1][2][3]. The incidence of AML increases with age, with the mean age at diagnosis between 65 and 70 years [1][2][3].…”

“…Acute myeloid leukemia (AML) is one of the most prevalent types of blood malignancies, although overall it is a rare orphan malignancy [1][2][3]. The incidence of AML increases with age, with the mean age at diagnosis between 65 and 70 years [1][2][3]. Remission rates in older patients (aged ≥ 60 years) are lower and relapse rates are higher, typically resulting in death within weeks or months of diagnosis [4,5].…”

“…In a population-based study in the USA, only 38.6% of 5480 patients with AML received chemotherapy within 3 months of diagnosis [13]. Older patients have a higher incidence of comorbidities and adverse molecular and cytogenetic abnormalities, and are at a higher risk for treatment-related morbidity and mortality, all of which contribute to a generally poorer prognosis [2,3,14]. As well as impacting treatment decisions, these clinical factors may negatively affect health-related quality of life (HRQoL) [15].…”