Background:Relapsed or Refractory acute myeloid leukemia (R/R AML) carries a poor prognosis with currently no standard salvage therapy. Intensive chemotherapy followed by allogeneic hematopoietic cell transplantation (allo-HSCT) represents the most common treatment approach. The CLAG ± M/I regimen [cladribine, cytarabine, granulocyte colony-stimulating factor (G-CSF) ± mitoxantrone or idarubicin] is a common utilized chemotherapy regimen. Mitoxantrone hydrochloride liposome (Lipo-MIT), the first approved nano-formulation of mitoxantrone, has demonstrated improved pharmacokinetics and shown anti-leukemic activity in early-phase AML studies. Building on retrospective safety and preliminary efficacy data of Lipo-MIT combined with CLAG (EHA 2024 Abstract P1749), we present interim single-arm findings (ChiCTR2400086291) assessing this therapeutic approach.

Methods: Eligible patients (pts) were aged 18-60 years old with confirmed diagnosis of R/R AML, except acute promyelocytic leukemia (APL). Pts received the Lipo-MIT (18 mg/m^2, day 1) combined with CLAG (cladribine 5 mg/m^2 days 1–5, cytarabine 1 g/m^2 days 1–5, G-CSF 300 μg days 0–5) every 4 weeks for up to 2 cycles. The primary endpoint was the composite complete remission (CRc) rate. Secondary endpoints were overall response rate (ORR), survival, minimal residual disease (MRD) negative rate, and safety.

Results: At data cut-off on June 2025, 27 patients (median age 43 years, range 10–59; 66.7% male) with R/R AML were enrolled, including refractory (59.3%, 16/27) and relapsed (40.7%, 11/27) disease; 11.1% (3/27) had secondary AML. ELN 2022 risk stratification revealed 14.8% favorable, 29.6% intermediate, and 55.6% adverse. The most frequently mutated genes were CEBPA (11.1%, 3/27), followed by FLT3-ITD, TP53, ASXL1 and U2AF1 (each 7.4%, 2/27). Among all 27 efficacy-evaluable pts, the CRc rate and ORR after one cycle were 63.0% (17/27) and 70.4% (19/27), respectively. Among CRc patients, the flow cytometric MRD negative rate after one cycle was 80.0% (12/15). Seven pts received 2 cycles of treatment, all of whom achieved CRc and flow cytometric MRD negative after two cycles. With a median follow-up of 3.3 months (range 0.4–18.6), the 6-month relapse-free survival (RFS) and overall survival (OS) rates were 80.8% and 71.4%, respectively. Of CRc patients who completed therapy, 4 underwent HSCT directly, 2 received consolidation followed by HSCT, and 9 did not receive further therapy. The 6-month RFS and OS rates of 6 patients who received HSCT were both 100%, and the 6-month RFS and OS rates of 10 patients who did not receive HSCT were both 66.7%. The common grade 3/4 treatment-related adverse events were mainly hematological toxicity, including leucopenia (100.0%), neutropenia (100.0%), thrombocytopenia (100.0%), anemia (48.1%), and febrile neutropenia (55.6%). Among 16 CRc pts, the median duration of neutrophil counts＜0.5×10^9 was 25 days (range 14–66) and platelet counts＜25×10^9 was 17 days (range 3–53).

Conclusions: Lipo-MIT combined with CLAG regimen showed a promising efficacy and manageable safety in R/R AML. The favorable post-transplant survival suggests this regimen is effective to bridge R/R AML patients to HSCT. The trial is still ongoing.

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2025
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