title: Salvage therapy using FLT3 inhibitors may improve long-term outcome of relapsed or refractory AML in patients with FLT3-ITD.
abstract: To determine the long-term efficacy of FLT3 inhibitors (FLT3i) in the salvage setting for relapsed and refractory (rel/ref) acute myeloid leukemia (AML) with FLT3 internal tandem duplication (AML FLT3-ITD), we conducted a retrospective study of 120 patients with rel/ref AML FLT3-ITD who received salvage therapy with either FLT3i-containing regimen (FLT3i group, N = 45) or conventional cytotoxic regimen (conventional group, N = 75). The median overall survival (OS) after the first salvage in the FLT3i group was 6·9 vs. 4·6 months in the conventional group (P = 0·17). The OS was better in the FLT3i group among patients with initial complete remission (CR) duration ≤12 months or with primary refractory disease (6·9 vs. 3·7 months; P < 0·01). The OS was better when FLT3i was combined with cytotoxic agents versus monotherapy (17 vs. 4·8 months; P = 0·017). Multivariate analysis revealed that the use of FLT3i was an independent predictor of OS (hazard ratio 0·58; 95% confidence interval, 0·38-0·88). Incorporating FLT3i into salvage strategies may improve long-term outcome of patients with AML FLT3-ITD. Prospective studies to validate this conclusion are warranted.
authors.affiliation: Divison of Cancer Medicine, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.|Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.
authors.forename: Hagop
authors.initials: H
authors.lastname: Kantarjian
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.
authors.forename: Naveen
authors.initials: N
authors.lastname: Pemmaraju
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.
authors.forename: Gautam
authors.initials: G
authors.lastname: Borthakur
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.
authors.forename: Stefan
authors.initials: S
authors.lastname: Faderl
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.
authors.forename: Guillermo
authors.initials: G
authors.lastname: Garcia-Manero
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.
authors.forename: Sherry
authors.initials: S
authors.lastname: Pierce
authors.affiliation: Department of Hematopathology, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.
authors.forename: Rajyalakshmi
authors.initials: R
authors.lastname: Luthra
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.
authors.forename: Marylou
authors.initials: M
authors.lastname: Cardenas-Turanzas
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Estrov
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.
authors.forename: Farhad
authors.initials: F
authors.lastname: Ravandi
authors.affiliation: Department of Leukemia, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.
authors.forename: Jorge
authors.initials: J
authors.lastname: Cortes
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D004341:Drug Evaluation / Q000379:methods; D005260:Female; D020440:Gene Duplication; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D012008:Recurrence; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods; D016019:Survival Analysis; D020080:Tandem Repeat Sequences / Q000235:genetics; D016896:Treatment Outcome; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors* / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3