Dataset Information

FLT3 inhibitors as maintenance therapy post allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients with FLT3 mutations: A meta-analysis.

ABSTRACT:

Background

Acute myeloid leukemia (AML) patients with a Fms-like tyrosine kinase 3 (FLT3) mutation have a high incidence of relapse despite allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a subsequent poor prognosis. FLT3 inhibitors (FLT3i) have been suggested to reduce the post-transplant relapse risk in recent studies. As more evidence is accumulated, we perform the present meta-analysis to assess the efficacy and safety of FLT3i as post-transplant maintenance therapy in AML patients.

Methods

Literature search was performed in public databases from inception to December 31, 2021. Overall survival (OS), relapse-free survival (RFS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), graft-versus-host disease (GVHD) and adverse events were compared between FLT3i and control groups. Pooled hazard ratio (HR) or relative risk (RR) with corresponding 95% confidence interval (CI) were calculated.

Results

We identified 12 eligible studies with 2282 FLT3-mutated AML patients who had received HSCT. There was no between-study heterogeneity and a fix-effect model was used. Post-transplant FLT3i maintenance significantly prolonged OS (HR = 0.41, 95%CI: 0.32-0.52, p < 0.001) and RFS (HR = 0.39, 95%CI 0.31-0.50, p < 0.001), and reduced CIR (HR = 0.31, 95%CI 0.20-0.46, p < 0.001) as compared with control. There were no significant risk differences in NRM (RR = 0.69, 95%CI 0.41-1.17, p = 0.169), acute GVHD (RR = 1.17, 95%CI 0.93-1.47, p = 0.175), chronic GVHD (RR = 1.31, 95%CI 0.91-1.39, p = 0.276) and grade ≥3 adverse events between both groups, except for skin toxicity (RR = 5.86, 95%CI 1.34-25.57, p = 0.019).

Conclusion

Post-transplant FLT3i maintenance can improve survival and reduce relapse in FLT3-mutated AML patients and is tolerable.

SUBMITTER: Fei X

PROVIDER: S-EPMC10067110 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Publications

FLT3 inhibitors as maintenance therapy post allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients with FLT3 mutations: A meta-analysis.

Fei Xinhong X Zhang Shuqin S Gu Jiangying J Wang Jingbo J

Cancer medicine 20221121 6

<h4>Background</h4>Acute myeloid leukemia (AML) patients with a Fms-like tyrosine kinase 3 (FLT3) mutation have a high incidence of relapse despite allogeneic hematopoietic stem cell transplantation (allo-HSCT) and a subsequent poor prognosis. FLT3 inhibitors (FLT3i) have been suggested to reduce the post-transplant relapse risk in recent studies. As more evidence is accumulated, we perform the present meta-analysis to assess the efficacy and safety of FLT3i as post-transplant maintenance therap ...[more]

PMID: 36411731

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Project description:BackgroundDisease relapse remains the major cause of death among patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who receive an allogeneic hematopoietic cell transplant (allo-HCT). Maintenance treatment with FLT3 inhibitors and hypomethylating agents (HMA) has been studied in various clinical trials with mixed results.ObjectiveTo synthesize the current evidence on the efficacy and safety of FLT3 inhibitors and HMA for maintenance therapy after allo-HCT in AML and MDS.MethodsFor this systematic review and meta-analysis Cochrane Library, Google Scholar, Ovid Medline, Ovid Embase, PubMed, Scopus, and Web of Science Core Collection were searched from inception to March 2021 for studies on maintenance therapies after allo-HCT in AML and MDS. Studies were excluded if they were reviews, commentaries, case series with <5 patients, or basic research articles, not published in English, not on post-allo-HCT maintenance with FLT3 inhibitors or HMA in AML or MDS, or if they were clinical trials without published results or duplicate publications from the same patient cohort. Studies with insufficient reporting of the primary endpoint (2-year overall survival [OS]) and studies using FLT3 inhibitors or HMA for pre-emptive treatment of imminent relapse based on positive measurable residual disease testing were excluded. Random-effects models were used to pool response rates for the primary outcome of 2-year OS. Hazard ratios (HR) for death and relapse were calculated for studies that included a control group. Rates of relapse-free survival (RFS), non-relapse mortality, and acute and chronic graft-versus-host-disease (GVHD) were studied as secondary endpoints. Downs and Black checklist and risk of bias assessments were used to gauge the quality of individual studies. The study protocol has been registered on PROSPERO (CRD42020187298).ResultsOur search strategy identified 5559 studies. Twenty-one studies with a total of 809 patients were included in the meta-analysis. The 2-year OS rates were 81.7% (95% confidence interval [CI], 73.8%-87.7%) and 65.7% (95% CI, 55.1%-74.9%) among patients treated with FLT3 inhibitors and HMA, respectively. In sensitivity analyses restricted to studies that included a control group, maintenance therapy with FLT3 inhibitors (HR for death = 0.41; 95% CI, 0.26-0.62) or HMA (HR = 0.45; 95% CI, 0.31-0.66) appeared superior to no maintenance therapy. The 2-year RFS rates were 79.8% (95% CI, 75.0%-83.9%) and 62.4% (95% CI, 50.6%-72.9%) among patients treated with FLT3 inhibitors and HMA, respectively. Rates of any grade acute and chronic GVHD were 33.1% (95% CI, 25.4%-41.8%; grade 3/4: 16.5%) and 42.5% (95% CI, 26.3%-60.4%) among FLT3 inhibitor and 42.7% (95% CI, 33.5%-52.4%; grade 3/4: 8.1%) and 41.5% (95% CI, 32.0%-51.6%) among HMA-treated patients, respectively.ConclusionMaintenance therapy with either FLT3 inhibitors or HMA after allo-HCT can lead to prolonged and improved OS and RFS with a favorable safety profile. Additional studies are needed to define the optimal duration of treatment, the role of measurable residual disease status, and transplant characteristics in patient selection.

Dataset Information

FLT3 inhibitors as maintenance therapy post allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients with FLT3 mutations: A meta-analysis.

Background

Methods

Results

Conclusion

Publications

FLT3 inhibitors as maintenance therapy post allogeneic hematopoietic stem cell transplantation in acute myeloid leukemia patients with FLT3 mutations: A meta-analysis.

Similar Datasets

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