Abstract
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.
Highlights
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy derived from hematopoietic stem cells with a series of abnormalities on the level of cytogenetics, genetics, and epigenetics [1, 2]
To reflect the increasing interest within clinical and basic research, we aimed to systematically review the current body of literature and to 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)
N, number; TKI, tyrosine kinase inhibitor; HSCT, hematopoietic stem-cell transplantation; MAC, myeloablative conditioning; RIC, reduced intensity conditioning; CR, complete remission; NR, not reported. aThe original number of patients in the study was 284, here we report on the subgroup analyses of patients that underwent midostaurin maintenance after stem-cell transplantation or not. bAs reported in the patient characteristics of the trials. cInclusion criteria, age distribution not given
Summary
Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy derived from hematopoietic stem cells with a series of abnormalities on the level of cytogenetics, genetics, and epigenetics [1, 2] Prognosis of this disease varies widely according to mutation profile, patient age, and comorbidities [2, 3]. In the front-line setting of FLT3-mutated AML, combining conventional chemotherapy with a multi-targeted tyrosine kinase inhibitor (TKI), namely midostaurin, resulted in improved overall survival [9]. Another multi-targeted TKI, sorafenib, has been approved for solid tumors such as hepatocellular and renal cell cancer [10, 11], but it has shown efficacy in terms of prolonged progression-free survival in younger AML patients in combination with upfront chemotherapy [12], but not in the elderly population [13]. When patients with FLT3-ITD-mutated AML relapsing after allogeneic stem-cell transplantation received sorafenib, the outcome may differ profoundly, as suggested by long-term remissions in selected patients [19, 20]
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