Treatment outcomes and unmet needs in patients with acute myeloid leukemia (AML) who are ineligible for intensive induction chemotherapy (IC): A systematic literature review (SLR).

AML is an aggressive cancer that accounts for around one third of all leukemias. Approximately 42% of patients with AML are ineligible for first-line (1L) IC, representing a vulnerable population with limited treatment options and poor outcomes. This SLR aimed to synthesize current evidence on clinical, economic, and patient-reported outcomes of available interventions. An SLR was conducted (PROSPERO: CRD420251034510) in accordance with NICE, Cochrane, and PRISMA guidelines. Databases and key congress presentations were searched for studies published from 2015-25 and 2023-25, respectively. Ineligibility for IC was defined as age ≥75, receipt of AML 1L treatments other than IC, or explicit statement of IC ineligibility. Clinical outcomes (e.g., efficacy/safety), economic burden, and patient experiences and patient-reported outcomes were assessed. Data were synthesized narratively due to heterogeneity of the study types and patient populations. The clinical outcome analysis identified 55 trials reporting efficacy/safety. Of the 32 randomized controlled trials (RCTs), most studies (n=27) evaluated treatments involving hypomethylating agents (HMAs; azacitidine [n=14] or decitabine [n=5]) and low-dose cytarabine (LDAC; n=8). Efficacy/safety outcomes were generally improved across studies for combinations vs monotherapies. Among RCT studies included in the safety analysis, only 2 studies reported hematological treatment-related adverse events (AEs). The 38 studies included in the economic burden analysis showed that the main drivers of direct costs included costs of drug administration, hospitalization, transfusion, and AE management. As expected, oral therapies (eg, venetoclax and hydroxycarbamide) had lower costs associated with drug administration than intravenous therapies (eg, LDAC). Indirect costs and productivity losses were substantial but less frequently studied. Analysis of patient-reported outcomes showed that fatigue, anxiety, and depression were present at baseline and generally improved or did not worsen following non-IC treatment. None of the included studies reported quantitative data on caregiver burden, highlighting a gap in the literature. Patients with AML who are ineligible for IC face significant clinical, economic, and disease burden challenges. Further research and novel oral regimens that can provide optimal, patient-centered, and economically sustainable care are essential for this high-need population.

Duke Scholars

Author Thomas William LeBlanc Medicine, Hematologic Malignancies and Cellular Therapy