TKI Maintenance After Stem-Cell Transplantation for FLT3-ITD Positive Acute Myeloid Leukemia: A Systematic Review and Meta-Analysis

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 -