Mitoxantrone liposome plus cytarabine and azacitidine for newly diagnosed Acute Myeloid Leukemia: A prospective, multicenter, randomized controlled study

Abstract

Abstract Abstract introductionAcute myeloid leukemia (AML) is a genetically diverse type of blood cancer, making up around 70% of all acute leukemia diagnoses. daunorubicin or idarubicin, with the antimetabolite cytarabine—often known as the 7+3 regimen—which results in a complete remission (CR) rate of roughly 60%. Nevertheless, research indicates that despite achieving remission, 40% to 50% of AML patients ultimately experience disease recurrence. Mitoxantrone liposome (Mito-L) is a novel formulation in which mitoxantrone is encapsulated within liposomes, thereby modifying its pharmacokinetics and tissue distribution. This formulation enables targeted accumulation in tumor tissues, prolongs the drug's half-life, and enhances its antitumor activity. In earlier phase II clinical trials Mito-L enhances tumor targeting and overcomes anthracycline resistance (phase II PTCL/NKTCL data: ORR 42.9%),Encouraged by these findings, we have introduced this liposomal formulation of mitoxantrone into the clinical management of AML. To evaluate the efficacy and safety of a novel Mito-L-based regimen (MA+AZA: Mito-L + cytarabine + azacitidine) versus traditional DA+AZA (daunorubicin + cytarabine + azacitidine) as induction therapy for newly diagnosed acute myeloid leukemia (AML). (ClinicalTrials.gov NCT06345365) Methods Adults (≥18y) with untreated AML (ECOG PS≤2, adequate organ function) were randomized 1:1 to receive MA+AZA or traditional DA+AZA. The experimental group received Mito-L (24 mg/m² day 1) + cytarabine (100 mg/m²days 1-3) + azacitidine (100 mg days 1-7). The control group received daunorubicin (60 mg/m²days 1-3) + cytarabine/azacitidine (doses identical to experimental group). Primary endpoint: complete remission (CR) rate per ELN 2022 criteria. Secondary endpoints included composite CR (CRc), objective response rate (ORR), adverse events (AEs), event-free survival (EFS), and overall survival (OS). Statistical analyses used intention-to-treat (ITT) with t-tests for continuous variables and χ² tests for categorical variables (α=0.05),P < 0.05 was considered statistically significant. ResultsAs of July 15, 2025, 22 pts with AML were randomized: MA+AZA, n=11; DA+AZA, n=11. Baseline demographics were similar between arms:median age 52 y (range, 27-68); 59.1% male;Median bone marrow blasts at diagnosis 52.0% (range: 9.5%–97.0%);45.5% AUER body positivity; 18.2% showed undetectable CD34 expression；31.8% exhibiting severe thrombocytopenia (<30 × 10⁹/L)；27.3% had leukocytosis >100 × 10⁹/L. At data cutoff, pts in MA+AZA and DA+AZA arms had 45.5% and 36.4% were still on tx,54.5% and 63.6% had discontinued tx, primarily due to disease progression (33.3% and 42.9%). CR at the end of treatment in the MA+AZA group was higher as the DA+AZA group (72.7% VS 63.6%,P<0.05), no-remission rate was lower vs DA+AZA (18.2% VS 27.3%; P<0.05). A similar rate of tx-emergent adverse events (TEAEs) (99% VS 99%), grade (gr) 3 or 4 AEs (72.7% VS 81.8%), and serious AEs (9.1% VS 27.3%) were observed with MA+AZA and DA+AZA, respectively. Most common gr 3 or 4 AEs with MA+AZA vs DA+AZA were myelosuppression (100% VS 100%), infection(36.4% VS 54.5%), liver events（9.1% VS 9.1%)，cardiovascular events (9.1% VS 0%). No treatment-related deaths were reported. ConclusionThe MA+AZA regimen shows encouraging efficacy and manageable toxicity in newly diagnosed AML. Preliminary efficacy was observed, with ongoing sample size expansion and follow-up extension to evaluate long-term survival outcomes