Efficacy and Safety of Mitoxantrone Hydrochloride Liposome Combined with Etoposide and Cytarabine in the Treatment of Newly Diagnosed Acute Myelomonocytic Leukemia or Acute Monocytic Leukemia

Background:Patients with acute myelomonocytic leukemia (AML-M4) and acute monocytic leukemia (AML-M5) often have high white blood cell counts, high-risk cytogenetics，progresse rapidly and the complete remission rate is low，therefore, most patients have a poor prognosis. Mitoxantrone is an effective drug for AML. Conventional mitoxantrone is often associated with bone marrow and cardiac toxicity, limiting its use. Mitoxantrone hydrochloride liposome (L-MIT）is an improved drug preparation that can be selectively enriched in tumor tissues, thereby enhancing antitumor activity and reducing its toxicity. At present, there are no reports about the treatment of newly diagnosed AML-M4 or AML-M5 with MEA regimen consisting of L-MIT(M),etoposide (E) and cytarabine (A) .

Methods: The study was approved by the Ethics Committee of Hebei University Affiliated Hospital.16 patients with newly diagnosed AML-M4/5 admitted to the Affiliated Hospital of Hebei University from August 2023 to May 2024 were retrospectively analyzed. All patients were treated with L-MIT-based MEA regimen( L-MIT 20 mg/m² d1, etoposide 100 mg d1-5, cytarabine 100 mg/m² d1-5). The clinical characteristics were analyzed retrospectively. The composite complete response (CRc) rate, total response rate (ORR) and adverse event rate were evaluated after 1 cycle of treatment. Adverse events were assessed by the common terminology criteria for adverse events (CTCAE) version 5.0.

Results: Among the 16 patients, there were 7 males and 9 females, with a median age of 45.2(24-68) years. Fit was assessed by Ferara in all patients, ECOG score of 0-2(0 in 3 cases, 1 in 8 cases, 2 in 5 cases). The average white blood cell count was 75.8(1.9-212.0) × 10⁹/L at diagnosis, including 6 patients with hyperleukocytic acute myeloid leukemia (WBC≥100×10⁹/L) , and all of them were detected by fusion gene and next generation sequencing, there were 4 cases (25.0%) with favorable prognosis, 5 cases (31.3%) with intermediate prognosis, 7 cases (43.8%) with adverse prognosis, 10 cases (62.5%) with FLT3 mutation, 5 cases (31.3%) with NPM1 mutation and 5 cases (31.3%) with PTPN11 mutation, there were 4 KRAS mutations (25.0%) , 3 DNMT3A mutations (18.8%) , 6 MLL rearrangements (37.5%) and CBFβ-MYH11 was found in 2 patients (12.5%) . Except one patient gave up the treatment, 15 patients were evaluated with ORR 93.3% , CRc 73.3% and PR 20.0% . 6 patients with hyperleukocytic acute myeloid leukemia, ORR100% , CRc66.7% , PR 33.3% , and 6 patients with MLL rearrangement, ORR 83.3% , CRc 66.7% . In 10 patients with FLT3 mutation, ORR was 90.0% , CRc was 60.0% , PR30.0% . The most common grade 3 and 4 adverse events were decreased neutrophil count(86.7%) , thrombocytopenia (80.0%) , anemia (66.7%) , granulocytic fever (73.3%) , and pulmonary infection (20.0%) . The other Grade 1 and 2 adverse events were skin and soft tissue infection (26.7%) , gastrointestinal bleeding (6.7%) , bluish skin (6.7%) , nausea and vomiting (33.3%). No liver, kidney and heart function damage, no infusion reaction.

Conclusion: AML-M4/5 patients are mostly in the intermediate to adverse prognosis group. L-MIT-based MEA regimen is effective and tolerable in the treatment of newly diagnosed AML-M4/5 patients. In patients with hyperleukocytic AML or with MLL rearrangement and FLT3 mutation, MEA regimen may achieve better efficacy, more worthy of further clinical exploration.

No relevant conflicts of interest to declare.

Patients with acute myelomonocytic leukemia (AML-M4) and acute monocytic leukemia belong (AML-M5) often have high white blood cell counts, high-risk cytogenetics，progresse rapidly and the complete remission rate is low，therefore, most patients have a poor prognosis. Mitoxantrone is an effective drug for AML. Conventional mitoxantrone is often associated with bone marrow and cardiac toxicity, limiting its use. Mitoxantrone hydrochloride liposome (L-MIT）is an improved drug preparation that can be selectively enriched in tumor tissues, thereby enhancing antitumor activity and reducing its toxicity. The aim of this study was to retrospectively analyze the efficacy and safety of L-MIT-based MEA regimen in the treatment of newly diagnosed acute myeloid leukemia (AML-M4) or acute monocytic leukemia (AML-M5) .