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Sorafenib and omacetaxine mepesuccinate as a safe and effective treatment for acute myeloid leukemia carrying internal tandem duplication of Fms-like tyrosine kinase 3.

  • Zhang, Chunxiao1
  • Lam, Stephen S Y1
  • Leung, Garret M K1
  • Tsui, Sze-Pui2
  • Yang, Ning1
  • Ng, Nelson K L1
  • Ip, Ho-Wan2
  • Au, Chun-Hang3
  • Chan, Tsun-Leung3
  • Ma, Edmond S K3
  • Yip, Sze-Fai4
  • Lee, Harold K K5
  • Lau, June S M6
  • Luk, Tsan-Hei6
  • Li, Wa7
  • Kwong, Yok-Lam1
  • Leung, Anskar Y H1
  • 1 Division of Haematology, Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. , (China)
  • 2 Division of Haematology, Department of Pathology, Queen Mary Hospital, Hong Kong, China. , (China)
  • 3 Department of Pathology, Hong Kong Sanatorium and Hospital, Hong Kong, China. , (China)
  • 4 Department of Medicine, Tuen Mun Hospital, Hong Kong, China. , (China)
  • 5 Department of Medicine, Princess Margaret Hospital, Hong Kong, China. , (China)
  • 6 Department of Medicine, Queen Elizabeth Hospital, Hong Kong, China. , (China)
  • 7 Department of Clinical Oncology, Prince of Wales Hospital, Hong Kong, China. , (China)
Published Article
Wiley (John Wiley & Sons)
Publication Date
Jan 15, 2020
DOI: 10.1002/cncr.32534
PMID: 31580501


Omacetaxine mepesuccinate (OME) has antileukemic effects against acute myeloid leukemia (AML) carrying an internal tandem duplication of Fms-like tyrosine kinase 3 (FLT3-ITD). A phase 2 clinical trial was conducted to evaluate a combination treatment of sorafenib and omacetaxine mepesuccinate (SOME). Relapsed or refractory (R/R) or newly diagnosed patients were treated with sorafenib (200-400 mg twice daily) and OME (2 mg daily) for 7 (first course) or 5 days (second course onward) every 21 days until disease progression or allogeneic hematopoietic stem cell transplantation (HSCT). The primary endpoint was composite complete remission, which was defined as complete remission (CR) plus complete remission with incomplete hematologic recovery (CRi). Secondary endpoints were leukemia-free survival (LFS) and overall survival (OS). Thirty-nine R/R patients and 5 newly diagnosed patients were recruited. Among the R/R patients, 28 achieved CR or CRi. Two patients showed partial remission, and 9 patients did not respond. Among the 5 newly diagnosed patients, 4 achieved CR, and 1 achieved CRi. The median LFS and OS were 5.6 and 10.9 months, respectively. Prior Fms-like tyrosine kinase 3 (FLT3) inhibitor exposure (P = .007), 2 or more inductions (P = .001), and coexisting IDH2 (P = .008) and RUNX1 mutations (P = .003) were associated with lower CR/CRi rates. HSCT consolidation and deep molecular responses (defined as an FLT3-ITD variant allelic frequency [VAF] ≤ 0.1% or a nucleophosmin 1 [NPM1] mutant VAF ≤ 0.01%) were associated with better OS and LFS. Prior FLT3 inhibitor exposure and 2 or more inductions were associated with inferior LFS. SOME was safe and effective for R/R and newly diagnosed FLT3-ITD AML. © 2019 American Cancer Society.

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