1. Mitoxantrone enhances five-year event-free survival over liposomal daunorubicin in MRD-guided pediatric AML treatment.

2.High-risk patients identified by MRD guidance benefited from hematopoietic stem-cell transplantation.

Evidence Rating Level: 1(Excellent)

Study Rundown: The study was a phase 3 trial investigating the efficacy of mitoxantrone versus liposomal daunorubicin as induction therapy for pediatric acute myeloid leukemia (AML). Treatment allocation was determined by overall disease risk, assessed through MRD analysis using flow cytometry. The trial enrolled pediatric patients with AML. They were randomized to receive either mitoxantrone or liposomal daunorubicin (DNX) as induction therapy. Response to treatment was evaluated through measurable residual disease (MRD) assessment using flow cytometry, with patients stratified into standard-risk and high-risk groups based on their MRD status. Patients underwent consolidation therapy with high-dose cytarabine. Patients were then followed up for event-free survival (EFS) and overall survival (OS) outcomes.  The trial showed that patients receiving mitoxantrone had significantly higher event-free survival (EFS) compared to those receiving liposomal daunorubicin. Liposomal daunorubicin was associated with a higher cumulative incidence of relapse compared to mitoxantrone. There were no significant differences in (OS) between the two treatment groups. The study’s multicenter approach with standardized procedures is a major strength of this trial. Incorporating MRD assessment allows for a more precise evaluation of treatment response, aiding in risk stratification and treatment decision-making. The inclusion of both randomized and observational cohorts enhances the generalizability of the findings. The premature closure of one randomization arm due to discontinued production of DNX limits the completeness of the comparison between the two induction therapies. In conclusion, this phase 3 trial compared mitoxantrone and liposomal daunorubicin for pediatric AML induction therapy, finding better event-free survival with mitoxantrone

Click to read the study in Journal of Clinical Oncology

Relevant Reading: Effect of age and body weight on toxicity and survival in pediatric acute myeloid leukemia: Results from NOPHO-AML 2004

In-Depth [randomized controlled trial]: This study compared the efficacy of mitoxantrone and liposomal daunorubicin in pediatric AML induction therapy using a multicenter, randomized design. Pediatric AML patients were randomized to receive either mitoxantrone or liposomal DNX induction therapy, with response assessed via MRD analysis. Subsequent consolidation therapy involved high-dose cytarabine, followed by monitoring for EFS and OS outcomes. Patients were stratified based on MRD assessment, with 34% achieving MRD <0.1% with mitoxantrone compared to 31% with liposomal daunorubicin. Mitoxantrone demonstrated significantly better event-free survival (71.9% vs. 56.6%, p = 0.042) and lower cumulative incidence of relapse (18.8% vs. 35.1%, p = 0.012) compared to liposomal daunorubicin. However, overall survival did not significantly differ between the two treatments. In summary, this multicenter, randomized study lends support for the use of mitoxantrone over liposomal daunorubicin in patients with pediatric AML stratified using MRD.

Image: PD

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