Mitoxantrone Versus Liposomal Daunorubicin in Induction of Pediatric AML With Risk Stratification Based on Flow Cytometry Measurement of Residual Disease.

Autor: Tierens A; Laboratory Medicine Program, University Health Network, Toronto General Hospital, Toronto, ON, Canada., Arad-Cohen N; Department of Pediatric Hemato-Oncology, Rambam Health Care Campus, Haifa, Israel., Cheuk D; Department of Pediatrics and Adolescent Medicine, Hong Kong Children's Hospital and Hong Kong Pediatric Hematology and Oncology Study Group (HKPHOSG), Hong Kong, China., De Moerloose B; Department of Pediatric Hematology-Oncology, Ghent University Hospital, Gent, Belgium., Fernandez Navarro JM; Department of Pediatric Hemato-Oncology, Hospital Universitario y Politécnico La Fe, Valencia, Spain., Hasle H; Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark., Jahnukainen K; New Children's Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland., Juul-Dam KL; Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark., Kaspers G; Princess Maxima Center for Pediatric Oncology, Utrecht, the Netherlands.; Emma Children's Hospital, Amsterdam UMC, Vrije Universiteit Amsterdam, Pediatric Oncology, Amsterdam, the Netherlands., Kovalova Z; Department of Paediatric Oncology/Haematology, Children's Clinical University Hospital, Riga, Latvia., Lausen B; Department of Pediatrics and Adolescent Medicine, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark., Norén-Nyström U; Department of Clinical Sciences, Pediatrics, Umeå University, Umea, Sweden., Palle J; Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden., Pasauliene R; Center of Oncology and Hematology, BMT Unit, Vilnius University Children's Hospital, Vilnius, Lithuania., Jan Pronk C; Childhood Cancer Center, Skåne University Hospital, Lund, Sweden., Saks K; Department of Paediatrics, SA Tallinna Lastehaigla, Tallinn, Estonia., Zeller B; Department of Pediatrics, Oslo University Hospital, Oslo, Norway., Abrahamsson J; Institution for Clinical Sciences, Department of Pediatrics, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Jazyk: angličtina
Zdroj: Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2024 Jun 20; Vol. 42 (18), pp. 2174-2185. Date of Electronic Publication: 2024 Apr 11.
DOI: 10.1200/JCO.23.01841
Abstrakt: Purpose: Measurable residual disease (MRD) by using flow cytometry after induction therapy is strongly prognostic in pediatric AML, and hematopoietic stem-cell transplant (hSCT) may counteract a poor response. We designed a phase III study with intensified response-guided induction and MRD-based risk stratification and treated poor induction response with hSCT. The efficacy of liposomal daunorubicin (DNX) in induction was compared with mitoxantrone.
Methods: The study planned to randomly assign 300 patients, but the production of DNX ceased in 2017. One hundred ninety-four patients were randomly assigned to mitoxantrone or experimental DNX in induction 1. Ninety-three non-randomly assigned patients served as an observation cohort. Primary end point was fraction of patients with MRD <0.1% on day 22 after induction 1. Patients with MRD ≥15% after induction 1 or ≥0.1% after induction 2 or FLT3 -ITD with NPM1 wildtype were stratified to high-risk therapy, including hSCT.
Results: Outcome for all 287 children was good with 5-year event-free survival (EFS 5y ) 66.7% (CI, 61.4 to 72.4) and 5-year overall survival (OS 5y ) 79.6% (CI, 75.0 to 84.4). Overall, 75% were stratified to standard-risk and 19% to high-risk. There was no difference in the proportion of patients with MRD <0.1% on day 22 after induction 1 (34% mitoxantrone, etoposide, araC [MEC], 30% DNX, P = .65), but the proportion increased to 61% for MEC versus 47% for DNX ( P = .061) at the last evaluation before induction 2. EFS 5y was significantly lower, 56.6% (CI, 46.7 to 66.5) versus 71.9% (CI, 63.0 to 80.9), and cumulative incidence of relapse (CIR) was higher, 35.1% (CI, 25.7 to 44.7) versus 18.8% (CI, 11.6 to 27.2) for DNX. The inferior outcome for DNX was only in standard-risk patients with EFS 5y 55.3% (CI, 45.1 to 67.7) versus 79.9% (CI, 71.1 to 89.9), CIR 39.5% (CI, 28.4 to 50.3) versus 18.7% (CI, 10.5 to 28.7), and OS 5y 76.2% (CI, 67.2 to 86.4) versus 88.6% (CI, 81.4 to 96.3). As-treated analyses, including the observation cohort, supported these results. For all high-risk patients, 85% received hSCT, and EFS 5y was 77.7 (CI, 67.3 to 89.7) and OS 5y was 83.0 (CI, 73.5 to 93.8).
Conclusion: The intensification of induction therapy with risk stratification on the basis of response to induction and hSCT for high-risk patients led to improved outcomes. Mitoxantrone had a superior anti-leukemic effect than liposomal daunorubicin.
Databáze: MEDLINE
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