CPX-351 induces remission in newly diagnosed pediatric secondary myeloid malignancies

Secondary myelodysplastic syndromes and acute myeloid leukemia (sMDS/AML) are rare in children and adolescents and have a dismal prognosis. The mainstay therapy is hematopoietic cell transplantation (HCT), but there has been no innovation in cytoreductive regimens. CP X-351, a fixed 5:1 molar ratio...

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Bibliographic Details
Published in:Blood advances 2022-01, Vol.6 (2), p.521-527
Main Authors: Hu, Yixin, Caldwell, Kenneth J., Onciu, Mihaela, Federico, Sara M., Salek, Marta, Lewis, Sara, Lei, Shaohua, Zhang, Jinghui, Nichols, Kim E., Takemoto, Clifford M., Triplett, Brandon M., Farrar, Jason E., Rubnitz, Jeffrey E., Ribeiro, Raul C., Wlodarski, Marcin W.
Format: Article
Language:English
Subjects:
Adolescent
Aged
Child
Cytarabine - therapeutic use
Daunorubicin - therapeutic use
Humans
Leukemia, Myeloid, Acute - diagnosis
Leukemia, Myeloid, Acute - drug therapy
Neoplasms, Second Primary - drug therapy
Prospective Studies
Stimulus Report
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Summary:Secondary myelodysplastic syndromes and acute myeloid leukemia (sMDS/AML) are rare in children and adolescents and have a dismal prognosis. The mainstay therapy is hematopoietic cell transplantation (HCT), but there has been no innovation in cytoreductive regimens. CP X-351, a fixed 5:1 molar ratio of liposomal cytarabine to daunorubicin, has shown favorable safety and efficacy in elderly individuals with secondary AML and children with relapsed de novo AML. We report the outcomes of 7 young patients (6 with newly diagnosed sMDS/AML and 1 with primary MDS/AML) uniformly treated with CP X-351. Five patients had previously received chemotherapy for osteosarcoma, Ewing sarcoma, neuroblastoma, or T-cell acute lymphoblastic leukemia; 1 had predisposing genomic instability disorder (Cornelia de Lange syndrome) and 1 had MDS-related AML and multiorgan failure. The median age at diagnosis of myeloid malignancy was 17 years (range, 13-23 years). Patients received 1 to 3 cycles of CP X-351 (cytarabine 100 mg/m2 plus daunorubicin 44 mg/m2) on days 1, 3, and 5, resulting in complete morphologic remission without overt toxicity or treatment-related mortality. This approach allowed for adding an FLT3 inhibitor as individualized therapy in 1 patient. Six patients were alive and leukemia-free at 0.5 to 3.3 years after HCT. One patient died as a result of disease progression before HCT. To summarize, CP X-351 is an effective and well-tolerated regimen for cytoreduction in pediatric sMDS/AML that warrants prospective studies. •CPX-351 treatment is well tolerated and results in morphologic remission in newly diagnosed pediatric secondary myeloid malignancies.•Favorable outcomes are achieved despite the presence of high-risk genetic lesions and previous therapies. [Display omitted]
ISSN:2473-9529
2473-9537
DOI:10.1182/bloodadvances.2021006139