Response to upfront azacitidine in juvenile myelomonocytic leukemia in the AZA-JMML-001 trial

  • 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 as #NCT02447666.

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Author:Charlotte NiemeyerORCiDGND, Christian FlothoORCiDGND, Daniel LipkaORCiDGND, Jan StarýORCiD, Claudia RössigORCiDGND, André BaruchelORCiD, Thomas KlingebielORCiDGND, Concetta Micalizzi, Gérard Michel, Karsten NysomORCiD, Susana RivesORCiD, Markus Schmugge LinerORCiDGND, Marco ZeccaORCiD, Maximilian SchönungORCiDGND, Irith BaumannGND, Peter NöllkeORCiDGND, Bouchra Benettaib, Noha Biserna, Jennifer Poon, Mathew Simcock, Meera Patturajan, Daniel Menezes, Allison GaudyORCiD, Marry M. van den Heuvel-EibrinkORCiD, Franco LocatelliORCiDGND
Parent Title (English):Blood advances
Publisher:American Society of Hematology
Place of publication:Washington, DC
Document Type:Article
Date of Publication (online):2021/07/23
Date of first Publication:2021/07/23
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2022/07/18
Tag:Clinical Trials and Observations; Myeloid Neoplasia; azacitidine; cardiocerebral resuscitation; cardiopulmonary resuscitation; child; follow-up; hematopoietic stem cell transplantation; juvenile myelomonocytic leukemia; leukemia; mutation; pharmacokinetics
Page Number:8
First Page:2901
Last Page:2908
This work was supported by Bristol Myers Squibb. The authors received writing and editorial assistance from Emily Poulin, and Jacqueline Moy, of Excerpta Medica, funded by Bristol Myers Squibb.
Conflict-of-interest disclosure: C.M.N. has served in a consultancy or advisory role for Bristol Myers Squibb (BMS) and Novartis. C.R. has served in a consultancy or advisory role for Amgen, BMS, Celgene, EUSA Pharma, Genentech, Pfizer, Novartis, and Roche. A.B. has received honoraria from AstraZeneca, BMS, Jazz Pharmaceuticals, Novartis, and Servier; has served in a consultancy or advisory role for BMS, Jazz Pharmaceuticals, Novartis, and Servier; and has received research funding from Servier. K.N. has received honoraria from Bayer, and has served in a consultancy or advisory role for Bayer and Y-mABs Therapeutics Inc. B.B. and N.B. were employed by BMS and have equity ownership in BMS. J.P., M.S., and A.G. are employed by, and have equity ownership in, BMS. D.M. is employed by BMS. M.M.v.d.H.-E. is employed by the Princess Máxima Center for Pediatric Oncology (Utrecht, The Netherlands). F.L. has served in a consultancy or advisory role for Amgen, Bellicum Pharmaceuticals, Neovii, and Novartis; and has served on a speakers’ bureau for Amgen, Bluebird bio, Jazz Pharmaceuticals, Medac, Miltenyi Biotec, Novartis, and Takeda. The remaining authors declare no competing financial interests.
Data requests may be submitted to Celgene, a Bristol Myers Squibb company, at and must include a description of
the research proposal.
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0