PMID- 34150652
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230920
IS  - 2234-943X (Print)
IS  - 2234-943X (Electronic)
IS  - 2234-943X (Linking)
VI  - 11
DP  - 2021
TI  - Clinical Benefits and Safety of FMS-Like Tyrosine Kinase 3 Inhibitors in Various 
      Treatment Stages of Acute Myeloid Leukemia: A Systematic Review, Meta-Analysis, 
      and Network Meta-Analysis.
PG  - 686013
LID - 10.3389/fonc.2021.686013 [doi]
LID - 686013
AB  - BACKGROUND: Given the controversial roles of FMS-like tyrosine kinase 3 
      inhibitors (FLT3i) in various treatment stages of acute myeloid leukemia (AML), 
      this study was designed to assess this problem and further explored which FLT3i 
      worked more effectively. METHODS: A systematic review, meta-analysis and network 
      meta-analysis (NMA) were conducted by filtering PubMed, Embase, Cochrane library, 
      and Chinese databases. We included studies comparing therapeutic effects between 
      FLT3i and non-FLT3i group in AML, particularly FLT3(+) patients, or demonstrating 
      the efficiency of allogeneic hematopoietic stem cell transplantation (allo-HSCT) 
      in FLT3(+) AML. Relative risk (RR) with 95% confidence intervals (CI) was used 
      for estimating complete remission (CR), early death and toxicity. Hazard ratio 
      (HR) was used to assess overall survival (OS), event-free survival (EFS), 
      relapse-free survival (RFS) and cumulative incidence of relapse (CIR). RESULTS: 
      After addressing all criteria, 39 studies were eventually analyzed. Better CR was 
      accomplished by FLT3i in untreated AML (RR 0.88, p = 0.04) and refractory and 
      relapsed FLT3(+) AML (rrAML) (RR 0.61, p < 0.01) compared to non-FLT3i arm, 
      followed by improved survival (untreated AML: OS, HR 0.76; EFS, HR 0.67; RFS, HR 
      0.72; all p < 0.01; FLT3(+) rrAML: OS, HR 0.60, p < 0.01; RFS, HR 0.40, p = 
      0.01). In addition, allo-HSCT improved survival in FLT3(+) AML (OS, HR 0.53; EFS, 
      HR 0.50; RFS, HR 0.57; CIR, HR 0.26; all p < 0.01), which was further prolonged 
      by FLT3i administrated after allo-HSCT (OS, HR 0.45; RFS, HR 0.34; CIR, HR 0.32; 
      all p < 0.01). Additionally, FLT3i consistently improved OS (p < 0.05) regardless 
      of FLT3-ITD ratio, when compared to non-FLT3i group. Besides, FLT3i showed 
      significantly increased risk of thrombocytopenia, neutropenia, anemia, skin- and 
      cardiac-related adverse effects, increased alanine aminotransferase, and 
      increased risk of cough and dyspnea (p < 0.05). In NMA, gilteritinib showed the 
      highest probability for improved prognosis. CONCLUSIONS: FLT3i safely improved 
      prognosis in induction/reinduction stage of FLT3(+) AML and further boosted 
      survival benefits from allo-HSCT as maintenance therapy, suggesting better 
      prognosis if FLT3i is combined before and after allo-HSCT. In NMA, gilteritinib 
      potentially achieved the best prognosis, which should be identified in 
      direct trials.
CI  - Copyright (c) 2021 Xu, He and Yu.
FAU - Xu, Qingyu
AU  - Xu Q
AD  - Department of Hematology and Oncology, International Cancer Center, Shenzhen Key 
      Laboratory, Shenzhen University General Hospital, Shenzhen University Clinical 
      Medical Academy, Shenzhen University Health Science Center, Shenzhen, China.
AD  - Department of Hematology and Oncology, Medical Faculty Mannheim, Heidelberg 
      University, Mannheim, Germany.
FAU - He, Shujiao
AU  - He S
AD  - Department of Hematology and Oncology, International Cancer Center, Shenzhen Key 
      Laboratory, Shenzhen University General Hospital, Shenzhen University Clinical 
      Medical Academy, Shenzhen University Health Science Center, Shenzhen, China.
FAU - Yu, Li
AU  - Yu L
AD  - Department of Hematology and Oncology, International Cancer Center, Shenzhen Key 
      Laboratory, Shenzhen University General Hospital, Shenzhen University Clinical 
      Medical Academy, Shenzhen University Health Science Center, Shenzhen, China.
LA  - eng
PT  - Systematic Review
DEP - 20210603
PL  - Switzerland
TA  - Front Oncol
JT  - Frontiers in oncology
JID - 101568867
PMC - PMC8209493
OTO - NOTNLM
OT  - FLT3 inhibitor
OT  - acute myeloid leukemia
OT  - meta-analysis
OT  - network meta-analysis
OT  - response
OT  - survival
OT  - toxicity
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/06/22 06:00
MHDA- 2021/06/22 06:01
PMCR- 2021/01/01
CRDT- 2021/06/21 06:00
PHST- 2021/03/26 00:00 [received]
PHST- 2021/05/11 00:00 [accepted]
PHST- 2021/06/21 06:00 [entrez]
PHST- 2021/06/22 06:00 [pubmed]
PHST- 2021/06/22 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fonc.2021.686013 [doi]
PST - epublish
SO  - Front Oncol. 2021 Jun 3;11:686013. doi: 10.3389/fonc.2021.686013. eCollection 
      2021.