Time burden of treatment with parenteral hypomethylating agents in combination with venetoclax among patients with newly diagnosed Acute Myeloid Leukemia

Abstract INTRODUCTION: Standard of care for patients with newly diagnosed acute myeloid leukemia (AML) who are not eligible for intensive chemotherapy is a parenteral hypomethylating agent (HMA) - azacitidine or decitabine, also referred to as DNA methyltransferase inhibitors - combined with oral venetoclax. This regimen requires repeated HMA administration in a clinical setting over a cycle of 28 days, placing a substantial time burden on patients affected by the disease. The logistical demands of frequent clinic visits may negatively impact patient quality of life and contribute to early treatment discontinuation. Despite the wide adoption of HMA-venetoclax therapy, its time burden for patients remains poorly characterized. The goal of this study is to address this gap by quantifying the time burden associated with initiation of parenteral HMA combined with venetoclax in routine clinical practice among patients with newly diagnosed AML. METHODS: This is a retrospective study of adults with newly diagnosed AML initiated on parenteral HMA combined with venetoclax using the Humana Healthcare Research Database (01/2019–12/2024), a US claims database of Medicare Advantage beneficiaries. The index date was defined as the date of the first HMA administration up to 60 days after the first AML diagnosis and between October 16, 2020 and June 30, 2024; patients had a prescription fill for venetoclax in the 30-day window before or after the index date. A washout period of ≥12 months of continuous insurance eligibility before the first observed AML diagnosis was required to ensure patients were newly diagnosed. The period of 12 months of continuous insurance eligibility before the index date (i.e., baseline) was used to describe patient characteristics. Outcomes were described during the follow-up period, which spanned from the index date until the end of continuous insurance eligibility or data availability, for a maximum of 6 months. Time burden was defined as the number of distinct days with all-cause healthcare visits, including inpatient days, and days with emergency room (ER), outpatient, and other visits. Days with outpatient visits were further stratified into distinct days with HMA administration, transfusion support, other AML treatment administration-related visits or other outpatient visits. Time at home was defined as days not spent in an inpatient or ER setting for any cause, and without outpatient visits related to cancer care. RESULTS: A total of 737 patients with newly diagnosed AML were initiated on the HMA combined with venetoclax therapy. Mean age at initiation was 76.3 years; 55.4% were male, 83.2% were White, 10.7% were Black, and the rest had other or unknown race. Over a third (38.7%) had myelodysplastic syndrome (MDS) during the baseline period. The index HMA was azacitidine for 70.4% of patients and decitabine for 29.6%. Most patients (93.6%) received the index HMA in the outpatient setting, 4.2% in the inpatient setting, and 2.2% in other settings. During the mean follow-up period of 4.8 months, patients spent a mean of 12.9 days per month on all-cause healthcare visits, including 3.4 days spent in inpatient setting, 0.3 days in ER setting, and 9.2 days in outpatient setting. In terms of outpatient days, patients spent a mean of 3.8 days per month receiving HMA therapy, 1.0 days receiving transfusion support, and the rest of the outpatient time receiving other AML and non-AML care. Patients spent a mean of 18.6 days per month at home or receiving non-cancer-related outpatient care. CONCLUSIONS: Patients with newly diagnosed AML ineligible for intensive chemotherapy spend over a third of their time engaged in medical care, and a substantial portion of this time is dedicated to receiving HMA therapy. These findings highlight a substantial time burden among patients and a need for alternative effective treatment options to optimize the delivery of medical care.