TKI Maintenance After Stem-Cell Transplantation for FLT3-ITD Positive Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis
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TKI Maintenance After Stem-Cell Transplantation for FLT3-ITD Positive Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis. / Gagelmann, Nico; Wolschke, Christine; Klyuchnikov, Evgeny; Christopeit, Maximilian; Ayuk, Francis; Kröger, Nicolaus.
in: FRONT IMMUNOL, Jahrgang 12, 630429, 2021.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Review › Forschung
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TY - JOUR
T1 - TKI Maintenance After Stem-Cell Transplantation for FLT3-ITD Positive Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis
AU - Gagelmann, Nico
AU - Wolschke, Christine
AU - Klyuchnikov, Evgeny
AU - Christopeit, Maximilian
AU - Ayuk, Francis
AU - Kröger, Nicolaus
N1 - Copyright © 2021 Gagelmann, Wolschke, Klyuchnikov, Christopeit, Ayuk and Kröger.
PY - 2021
Y1 - 2021
N2 - This analysis aimed to systematically review and synthesize the existing evidence regarding the outcome of tyrosine kinase inhibitor (TKI) maintenance therapy after allogeneic stem-cell transplantation for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). We searched publicly available databases, references lists of relevant reviews, registered trials, and relevant conference proceedings. A total of 7 studies comprising 680 patients were included. Five studies evaluated sorafenib and 2 studies evaluated midostaurin, compared with control. The incidence of relapse was significantly reduced after TKI therapy, showing an overall pooled risk ratio (RR) of 0.35 (95% confidence interval [CI], 0.23-0.51; P < 0.001), with a marked 65% reduced risk for relapse. The overall pooled RR for relapse-free survival and overall survival showed significantly improved outcome after TKI maintenance therapy, being 0.48 (95% CI, 0.37-0.61; P < 0.001) and 0.48 (95% CI, 0.36-0.64; P < 0.001). The risk for relapse or death from any cause was reduced by 52% using TKI. No difference in outcome was seen for non-relapse mortality, and the risk for chronic or acute graft-vs. -host disease appeared to be increased, at least for sorafenib. In conclusion, post-transplant maintenance therapy with TKI was associated with significantly improved outcome in relapse and survival in patients with FLT3-ITD positive AML.
AB - This analysis aimed to systematically review and synthesize the existing evidence regarding the outcome of tyrosine kinase inhibitor (TKI) maintenance therapy after allogeneic stem-cell transplantation for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). We searched publicly available databases, references lists of relevant reviews, registered trials, and relevant conference proceedings. A total of 7 studies comprising 680 patients were included. Five studies evaluated sorafenib and 2 studies evaluated midostaurin, compared with control. The incidence of relapse was significantly reduced after TKI therapy, showing an overall pooled risk ratio (RR) of 0.35 (95% confidence interval [CI], 0.23-0.51; P < 0.001), with a marked 65% reduced risk for relapse. The overall pooled RR for relapse-free survival and overall survival showed significantly improved outcome after TKI maintenance therapy, being 0.48 (95% CI, 0.37-0.61; P < 0.001) and 0.48 (95% CI, 0.36-0.64; P < 0.001). The risk for relapse or death from any cause was reduced by 52% using TKI. No difference in outcome was seen for non-relapse mortality, and the risk for chronic or acute graft-vs. -host disease appeared to be increased, at least for sorafenib. In conclusion, post-transplant maintenance therapy with TKI was associated with significantly improved outcome in relapse and survival in patients with FLT3-ITD positive AML.
KW - Graft vs Host Disease/etiology
KW - Hematopoietic Stem Cell Transplantation/adverse effects
KW - Humans
KW - Leukemia, Myeloid, Acute/genetics
KW - Mutation
KW - Protein Kinase Inhibitors/therapeutic use
KW - Protein-Tyrosine Kinases/antagonists & inhibitors
KW - Recurrence
KW - fms-Like Tyrosine Kinase 3/genetics
U2 - 10.3389/fimmu.2021.630429
DO - 10.3389/fimmu.2021.630429
M3 - SCORING: Review article
C2 - 33790903
VL - 12
JO - FRONT IMMUNOL
JF - FRONT IMMUNOL
SN - 1664-3224
M1 - 630429
ER -