Omacetaxine mepesuccinate in the treatment of intractable chronic myeloid leukemia

Figures & data

Figure 1 The structure of omacetaxine mepesuccinate.

Notes: Drug name: omacetaxine mepesuccinate (SYNRIBO); Indication: Adult patients with CMP-CP or AP with resistance and/or intolerance to two or more TKIs; Chemical structure: 4-methyl (2R)-2-hydroxy-2-(4-hydroxy-4-methylpentyl) butanedioate (ester).
Abbreviations: CMP-CP, common myeloid progenitor-chronic phase; AP, accelerated phase; TKI, tyrosine kinase inhibitor.

Figure 2 The major mechanism of action of omacetaxine mepesuccinate.

Abbreviations: WT, wild type, CML, chronic myeloid leukemia; MCL-1, myeloid cell leukemia-1.

Table 1 Summary of OM related clinic trials

Therapy	Trials	Patients	CML phase	CHR (%)	Cytogenetic (%)	References
HHT/OM	8	464	Early or late CP	80	42 or 20.5	^Citation57,Citation58,Citation60,Citation62^–^Citation66
OM + Imatinib	2	24	CP	66	50	^Citation59,Citation67
HHT + ara-C	4	202	Early or late CP	81	ND	^Citation68,Citation69
HHT + IFN-α	1	37	Early CP	89	57	^Citation70
OM + Imatinib + G-CSF	1	11	BP	61	100	^Citation71
HHT + IFN-α + ara-C	1	90	Early CP	94	74	^Citation72

Abbreviations: CML, chronic myeloid leukemia; CHR, complete hematologic response, HHT, homoharringtonine; OM, Omacetaxine mepesuccinate; Ara-C, arabinofuranosyl cytidine; IFN-α, interferon-alpha; G-CSF, granulocyte colony-stimulating factor; CP, chronic phase; ND, not determined.

Table 2 Summary of current CML treatment

Name	Function	Mechanism of action
Imatinib	BCR-ABL kinase inhibitor	Specific for the tyrosine kinase domain in ABL, c-Kit and PDGF-R
Dasatinib	BCR-ABL kinase inhibitor	Targeting ABL, Src, c-Kit, ephrin receptors and serveral other tyrosine kinases
Nilotinib	2nd generation BCR-ABL kinase inhibitor	Targeting ABL, LCK, c-Kit, EPHA3, EPHA8, DDR1, DDR2, PDGF-R, MAPK11 and ZAK
Ponatinib	3rd generation BCR-ABL kinase inhibitor	Targeting BCR-ABL with or without T3151 mutation
Ara-C	Cytarabine or cytosine arabinoside	Interfering with DNA synthesis
IFN-α	Interferon α	Selective toxicity against the leukemic clone; enhancement of “immune” regulation; modulation of bone marrow microenvironment regulation of hematopoiesis
G-CSF	Granulocyte colony-stimulating factor	Overcome imatinib mesylate-induced neutropenia as myelosuppression

Abbreviations: Ara-C, arabinofuranosyl cytidine; IFN-α, interferon-alpha; G-CSF, granulocyte colony-stimulating factor.

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