Response to upfront azacitidine in juvenile myelomonocytic leukemia in the AZA-JMML-001 trial
| Autor: | Noha Biserna, André Baruchel, Jan Starý, Daniel B. Lipka, Claudia Rossig, Concetta Micalizzi, Irith Baumann, Gérard Michel, Jennifer Poon, Allison Gaudy, Franco Locatelli, Thomas Klingebiel, Marry M. van den Heuvel-Eibrink, Christian Flotho, Daniel Menezes, Peter Nöllke, Bouchra Benettaib, Meera Patturajan, Susana Rives, Maximilian Schönung, Karsten Nysom, Markus Schmugge Liner, Mathew Simcock, Marco Zecca, Charlotte M. Niemeyer |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Adult medicine.medical_specialty Clinical Trials and Observations medicine.medical_treatment Azacitidine Population Hematopoietic stem cell transplantation 03 medical and health sciences 0302 clinical medicine Pharmacokinetics Internal medicine medicine Clinical endpoint Humans ddc:610 education Child JMML education.field_of_study Juvenile myelomonocytic leukemia business.industry Hematopoietic Stem Cell Transplantation Hematology DNA Methylation medicine.disease Leukemia 030104 developmental biology Leukemia Myelomonocytic Juvenile Settore MED/38 - PEDIATRIA GENERALE E SPECIALISTICA 030220 oncology & carcinogenesis Mutation business Progressive disease medicine.drug |
| Zdroj: | blood advances r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu instname r-FSJD: Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu Fundació Sant Joan de Déu Blood Adv |
| ISSN: | 2473-9529 |
| Popis: | Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative therapy for most children with juvenile myelomonocytic leukemia (JMML). Novel therapies controlling the disorder prior to HSCT are needed. We conducted a phase 2, multicenter, open-label study to evaluate the safety and antileukemic activity of azacitidine monotherapy prior to HSCT in newly diagnosed JMML patients. Eighteen patients enrolled from September 2015 to November 2017 were treated with azacitidine (75 mg/m2) administered IV once daily on days 1 to 7 of a 28-day cycle. The primary end point was the number of patients with clinical complete remission (cCR) or clinical partial remission (cPR) after 3 cycles of therapy. Pharmacokinetics, genome-wide DNA-methylation levels, and variant allele frequencies of leukemia-specific index mutations were also analyzed. Sixteen patients completed 3 cycles and 5 patients completed 6 cycles. After 3 cycles, 11 patients (61%) were in cPR and 7 (39%) had progressive disease. Six of 16 patients (38%) who needed platelet transfusions were transfusion-free after 3 cycles. All 7 patients with intermediate- or low-methylation signatures in genome-wide DNA-methylation studies achieved cPR. Seventeen patients received HSCT; 14 (82%) were leukemia-free at a median follow-up of 23.8 months (range, 7.0-39.3 months) after HSCT. Azacitidine was well tolerated and plasma concentration-–time profiles were similar to observed profiles in adults. In conclusion, azacitidine monotherapy is a suitable option for children with newly diagnosed JMML. Although long-term safety and efficacy remain to be fully elucidated in this population, these data demonstrate that azacitidine provides valuable clinical benefit to JMML patients prior to HSCT. This trial was registered at www.clinicaltrials.gov as #NCT02447666. |
| Databáze: | OpenAIRE |
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