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Aims: Treatment of acute myeloid leukemia (AML) requires significant healthcare resource utilization (HRU), including lengthy hospitalizations. In a phase 3 study (NCT01696084), CPX-351 (Vyxeos) showed significant benefits to overall survival and complete remission versus conventional 7 + 3 cytarabine/daunorubicin. This analysis evaluated HRU in patients aged 60-75 years with newly diagnosed high-risk/secondary AML treated with CPX-351 versus 7 + 3 in the phase 3 study. Materials and methods: Patients were randomized to receive up to two induction cycles with CPX-351 or 7 + 3. Responders could receive up to two cycles of consolidation. To normalize HRU to length of treatment, patients were assessed on a per patient-year (PPY) basis. HRU analyses included hospital and intensive care unit (ICU) stays, anti-infective use, transfusions, and white blood cell colony-stimulating factor (CSF). Results: The median (range) total duration of hospitalization was 39 (3-110) days with CPX-351 ( n  = 153) and 32 (2-83) days with 7 + 3 ( n  = 151); the estimated durations of hospitalization PPY were 198.4 and 240.5 days, respectively. The median (range) total duration of ICU stays was 0 (0-45) days with CPX-351 and 0 (0-17) days with 7 + 3; the estimated durations of ICU stays PPY were 6.7 and 10.5 days, respectively. When comparing supportive care use during CPX-351 and 7 + 3 treatment, the estimated number PPY of bags of platelets used (24.6 vs 26.9, respectively), bags of packed red blood cells used (13.0 vs 13.9), days of anti-infectives (162.0 vs 159.2), and days of CSF (4.0 vs 2.4) were not notably different. Limitations: This clinical study analysis may not represent real-world HRU patterns or be generalizable to a broader AML population. Conclusions: These PPY data, showing shorter durations of hospitalization and similar use of supportive care with CPX-351 versus 7 + 3, suggest CPX-351 is not associated with increased HRU in older patients with newly diagnosed high-risk/secondary AML.