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

TitleSorafenib and omacetaxine mepesuccinate as a safe and effective treatment for acute myeloid leukemia carrying internal tandem duplication of Fms‐like tyrosine kinase 3
Authors
Keywordsacute myeloid leukemia (AML)
internal tandem duplication of Fms‐like tyrosine kinase 3 (FLT3‐ITD)
minimal residual disease
omacetaxine mepesuccinate
sorafenib
Issue Date2020
PublisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-0142
Citation
Cancer, 2020, v. 126 n. 2, p. 344-353 How to Cite?
AbstractBackground: 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). Methods: 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). Results: 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. Conclusions: SOME was safe and effective for R/R and newly diagnosed FLT3‐ITD AML.
Persistent Identifierhttp://hdl.handle.net/10722/289440
ISSN
2019 Impact Factor: 5.742
2015 SCImago Journal Rankings: 3.188
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, C-
dc.contributor.authorLam, SSY-
dc.contributor.authorLeung, GMK-
dc.contributor.authorTsui, SP-
dc.contributor.authorYang, N-
dc.contributor.authorNg, NKL-
dc.contributor.authorIp, HW-
dc.contributor.authorAu, CH-
dc.contributor.authorChan, TL-
dc.contributor.authorMa, ESK-
dc.contributor.authorYip, SF-
dc.contributor.authorLee, HKK-
dc.contributor.authorLau, JSM-
dc.contributor.authorLuk, TH-
dc.contributor.authorLi, W-
dc.contributor.authorKwong, YL-
dc.contributor.authorLeung, AYH-
dc.date.accessioned2020-10-22T08:12:42Z-
dc.date.available2020-10-22T08:12:42Z-
dc.date.issued2020-
dc.identifier.citationCancer, 2020, v. 126 n. 2, p. 344-353-
dc.identifier.issn0008-543X-
dc.identifier.urihttp://hdl.handle.net/10722/289440-
dc.description.abstractBackground: 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). Methods: 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). Results: 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. Conclusions: SOME was safe and effective for R/R and newly diagnosed FLT3‐ITD AML.-
dc.languageeng-
dc.publisherJohn Wiley & Sons, Inc. The Journal's web site is located at http://onlinelibrary.wiley.com/journal/10.1002/(ISSN)1097-0142-
dc.relation.ispartofCancer-
dc.rightsPreprint This is the pre-peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Postprint This is the peer reviewed version of the following article: [FULL CITE], which has been published in final form at [Link to final article using the DOI]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.-
dc.subjectacute myeloid leukemia (AML)-
dc.subjectinternal tandem duplication of Fms‐like tyrosine kinase 3 (FLT3‐ITD)-
dc.subjectminimal residual disease-
dc.subjectomacetaxine mepesuccinate-
dc.subjectsorafenib-
dc.titleSorafenib and omacetaxine mepesuccinate as a safe and effective treatment for acute myeloid leukemia carrying internal tandem duplication of Fms‐like tyrosine kinase 3-
dc.typeArticle-
dc.identifier.emailZhang, C: chunxiao@hku.hk-
dc.identifier.emailLam, SSY: slsy@HKUCC-COM.hku.hk-
dc.identifier.emailNg, NKL: kalamng@hku.hk-
dc.identifier.emailIp, HW: iphowan@hku.hk-
dc.identifier.emailMa, ESK: eskma@hku.hk-
dc.identifier.emailYip, SF: yipsf@HKUCC-COM.hku.hk-
dc.identifier.emailKwong, YL: ylkwong@hkucc.hku.hk-
dc.identifier.emailLeung, AYH: ayhleung@hku.hk-
dc.identifier.authorityChan, TL=rp00418-
dc.identifier.authorityKwong, YL=rp00358-
dc.identifier.authorityLeung, AYH=rp00265-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/cncr.32534-
dc.identifier.pmid31580501-
dc.identifier.scopuseid_2-s2.0-85073989878-
dc.identifier.hkuros317469-
dc.identifier.volume126-
dc.identifier.issue2-
dc.identifier.spage344-
dc.identifier.epage353-
dc.identifier.isiWOS:000488641300001-
dc.publisher.placeUnited States-
dc.identifier.issnl0008-543X-

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