Efficacy and safety of azacitidine plus LDAC in newly diagnosed, frail elderly patients with Acute Myeloid Leukemia

Abstract Effective treatment options remain limited for elderly patients with acute myeloid leukemia (AML) , particularly for those with significant frailty. This prospective phase 2 clinical trial evaluated efficacy and safety of azacitidine combined with low-dose cytarabine (LDAC) in newly diagnosed, frail elderly AML patients. As of June 30, 2025, we enrolled 38 patients aged ≥ 60 years who were deemed unsuitable for intensive chemotherapy. The treatment regimen consisted of subcutaneous azacitidine (75 mg/m2 daily on days 1-7) plus subcutaneous LDAC (20 mg twice daily on days 1-10) in 28-day cycles. Primary endpoint was overall response rate (ORR; defined as CR+CRi+MLFS); secondary endpoints included overall survival (OS), duration of response (DOR), safety and tolerability. Median age was 73.1 years (range, 62.2-85.4 years), and 15.8% had secondary AML. According to the 2022 ELN risk classifications, 8 (21.1%), 11 (28.9%) and 19 (50%) patients had favorable-risk, intermediate-risk and adverse-risk AML. Molecular profiling revealed myelodysplasia-related mutations in 36.8% of patients and TP53 mutations in 15.8%. No early death (within 30 days) was observed. ORR was 50% (19/38), median time to first response was 1.7 months, and among them 13 (68.4%) patients achieved MRD negative. Median follow-up duration was 14.6 (95% CI: 8.7-20.5) months and median number of treatment cycles delivered was 2 (range, 1-9). Median OS was 22.5 (95% CI 7.9-37.1) months and median DOR was 9.1 (95% CI: 6.07-12.13) months. Key grade ≥ 3 adverse events were febrile neutropenia (47.3%) and neutropenia (18.4%). Azacitidine plus LDAC exhibits favorable safety profiles and highly effective, and may be a promising option for frail elderly AML patients ineligible for intensive chemotherapy. This trial was registered at chictr.org.cn as ChiCTR2000035292.