title: Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukaemia in first complete remission.
abstract: We performed a retrospective study analysing the effect of sorafenib, an oral fms-Like Tyrosine Kinase 3 (FLT3)/multikinase inhibitor, as post-transplant maintenance in adult patients with FLT3-internal tandem duplication (ITD) acute myeloid leukaemia (AML). We identified consecutive patients with FLT3-ITD AML diagnosed between 2008 and 2014 who received haematopoietic cell transplantation (HCT) in first complete remission (CR1). Post-HCT initiation of sorafenib (yes/no) was evaluated as a time-varying covariate in the overall survival/progression-free survival (OS/PFS) analysis and we performed a landmark analysis of controls alive without relapse at the median date of sorafenib initiation. We identified 26 sorafenib patients and 55 controls. Median follow-up was 27·2 months post-HCT for sorafenib survivors, and 38·4 months for controls (P = 0·021). The median time to initiating sorafenib was 68 days post-HCT; 43 controls were alive without relapse at this cut-off. Sorafenib patients had improved 2-year OS in the d+68 landmark analysis (81% vs. 62%, P = 0·029). Sorafenib was associated with improved 2-year PFS (82% vs. 53%, P = 0·0081) and lower 2-year cumulative incidence of relapse (8·2% vs. 37·7%, P = 0·0077). In multivariate analysis, sorafenib significantly improved OS [Hazard ratio (HR) 0·26, P = 0·021] and PFS (HR 0·25, P = 0·016). There was no difference in 2-year non-relapse mortality (9·8% vs. 9·3%, P = 0·82) or 1-year chronic graft-versus-host disease (55·5% vs. 37·2%, P = 0·28). These findings suggest potential benefit of post-HCT sorafenib in FLT3-ITD AML, and support further evaluation of post-HCT FLT3 inhibition.
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.|Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Brunner
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Shuli
authors.initials: S
authors.lastname: Li
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Amir T
authors.initials: AT
authors.lastname: Fathi
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Martha
authors.initials: M
authors.lastname: Wadleigh
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Vincent T
authors.initials: VT
authors.lastname: Ho
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Kerry
authors.initials: K
authors.lastname: Collier
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Connolly
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Karen K
authors.initials: KK
authors.lastname: Ballen
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Corey S
authors.initials: CS
authors.lastname: Cutler
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Bimalangshu R
authors.initials: BR
authors.lastname: Dey
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Areej
authors.initials: A
authors.lastname: El-Jawahri
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Nikiforow
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: McAfee
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: John
authors.initials: J
authors.lastname: Koreth
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Deangelo
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Edwin P
authors.initials: EP
authors.lastname: Alyea
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Joseph H
authors.initials: JH
authors.lastname: Antin
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Spitzer
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Stone
authors.affiliation: Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soiffer
authors.affiliation: Massachusetts General Hospital, Boston, MA, USA. ychen6@partners.org.
authors.forename: Yi-Bin
authors.initials: YB
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D060046:Maintenance Chemotherapy; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D012074:Remission Induction; D012189:Retrospective Studies; D000077157:Sorafenib; D020080:Tandem Repeat Sequences; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult; D051941:fms-Like Tyrosine Kinase 3 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib; D051941:fms-Like Tyrosine Kinase 3
keywords: acute myeloid leukaemia; allogeneic transplantation; fms-Like Tyrosine Kinase 3; maintenance chemotherapy; sorafenib