Mitoxantrone hydrochloride liposome combined with cytarabine (MA) for patients with newly diagnosed secondary acute myeloid leukemia.

6533 Background: Secondary acute myeloid leukemia (sAML) is an aggressive subset typically characterized by unfavorable biological features. CPX-351, a dual-drug liposomal formulation of cytarabine and daunorubicin, has demonstrated improved remission rates and overall survival (OS) in sAML; however, its use remains limited in China. Mitoxantrone hydrochloride liposome (Lipo-MIT), a pegylated liposomal formulation of mitoxantrone, provides enhanced anti-tumor efficacy and reduced toxicity. Here we report the outcomes of a novel regimen combining Lipo-MIT and cytarabine (MA) for patients (pts) with newly diagnosed sAML. Methods: This is a single-arm, prospective, exploratory study. Eligible pts were aged 18 to 75 years and had newly diagnosed therapy-related AML, AML with antecedent myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML), or de novo AML with MDS-related cytogenetic abnormalities. Patients received MA regimen consisting of Lipo-MIT (24mg/m 2 on day 1) and cytarabine (100mg/m 2 /d from days 1 to 7) every four weeks for up to 2 cycles. The primary endpoint was CRc (complete remission (CR)+CR with incomplete neutrophil or platelet recovery (CRi) ). The secondary endpoints included the rate of CRc with negative minimal residual disease (MRD), overall response rate (ORR), overall survival (OS) and safety. Results: As of January 20, 2025, a total of 13 pts were enrolled with a median age of 53 years (range, 24.0-65.0), including 8 with therapy-related AML and 5 with AML arising from antecedent MDS. According to the 2022 edition of the European Leukemia Network recommendations, 2 (15.4%) pts were classified as a favorable prognosis, 2 (15.4%) as intermediate, 8 (61.5%) as adverse, and 1 (7.7%) as unknown. The most commonly mutated gene and abnormality karyotype was TP53 and del(7q), respectively, both occurring in 23.1% (3/13). Of 13 pts, 5 were assessed as CR, 3 as CRi and 1 as PR. The CRc rate was 61.5% (8/13) and the ORR was 69.2% (9/13). Among 8 pts who achieved CRc, the rate of negative MRD was 75% (6/8). With a median follow-up of 3.4 months, the 1-year OS rate was 88.9% (95% CI, 43.3-98.4) while the median OS was not reached. The median duration of absolute neutrophil count <500 cells/μL was 21.0 days (range, 7.0-29.0) and platelet count <50000 platelets/μL was 20.0 days (range, 14.0-61.0) in pts who achieved CRc after initial induction. The non-hematological treatment-emergent adverse events (TEAEs) graded at 3 were febrile neutropenia (46.2%), fever (7.7%), sepsis (7.7%), pulmonary infection (7.7%), oral mucositis (7.7%), anaphylaxis (7.7%) and pruritus (7.7%). No non-hematological TEAEs of grade 4 or worse were observed and the 60-day mortality rate was 0%. Conclusions: The MA regimen demonstrated encouraging remission rates and a superior safety profile, indicating its potential as a treatment option for newly diagnosed sAML. Clinical trial information: ChiCTR2300076618 .