首页|Gilteritinib为基础的方案桥接异基因造血干细胞移植对复发难治伴FLT3-ITD突变急性髓系白血病患者的疗效及安全性研究

Gilteritinib为基础的方案桥接异基因造血干细胞移植对复发难治伴FLT3-ITD突变急性髓系白血病患者的疗效及安全性研究

Efficacy and safety of gilteritinib-based combination therapy bridging allo-HSCT in relapsed or refractory acute myeloid leukemia patients with positive FLT3-ITD mutation

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目的 探讨Gilteritinib(Gilt)为基础的方案桥接异基因造血干细胞移植(allo-HSCT)对伴FMS样酪氨酸激酶3(FLT3)基因内部串联重复(ITD)突变的复发难治性急性髓系白血病(R/RAML)患者的安全性、有效性,以及移植后Gilt维持治疗对FLT3-ITD阳性R/R AML患者预后的影响.方法 回顾性分析2019年8月至2023年1月苏州大学附属第一医院收治的26例伴FLT3-ITD突变的R/R AML患者.统计所有纳入患者的复合完全缓解(CRc)率、总生存(OS)期、无病生存(DFS)期和不良反应.结果 26例FLT3-ITD突变阳性R/RAML患者中,男14例,女12例,中位年龄38(18~65)岁.难治18例,复发8例.用药第14~21天疗效:完全缓解(CR)率为26.9%(7/26),CR伴血液学不完全恢复(CRi)率为 57.7%(15/26),部分缓解(PR)率为 7.7%(2/26),CRc率为 84.6%(22/26),微小残留病(MRD)转阴率为65.4%.所有患者12、24个月累计OS率分别为79.0%和72.0%.中位OS期未达到.中位随访时间为16.0个月.全部治疗有效患者12、24个月累计DFS率分别为78.0%和71.0%.中位DFS期未达到.接受allo-HSCT的患者中位OS期未达到,较未接受allo-HSCT的患者(3.3个月,95%CI2.2~4.3个月)显著延长(P=0.005).移植后是否应用Gilt维持治疗的患者中位OS期均未达到,且移植后维持治疗的患者OS明显优于移植后未进行维持治疗的患者(P=0.019).本研究中FLT3-ITD基因突变清除率为38.5%,且FLT3-ITD基因突变转阴的患者中位OS期未达到,明显长于未转阴的患者(15.0个月)(P=0.018).Gilt为基础的方案最常见的3级及以上血液学不良反应包括白细胞减少(76.9%)、中性粒细胞减少(76.9%)、中性粒细胞减少性发热(61.5%)、血小板减少(69.2%)和贫血(57.7%).其中1例患者在移植后口服Gilt维持治疗时出现分化综合征,治疗后好转.结论 Gilt为基础的方案桥接allo-HSCT治疗FLT3-ITD突变阳性R/R AML患者的CRc率较高,MRD转阴率也较高,起效迅速,有效延长患者生存期.此外,FLT3-ITD基因突变清除率较高,且桥接移植和移植后Gilt维持治疗明显改善患者生存.治疗过程中不良事件的监测和管理至关重要.
Objective This study aims to evaluate the safety and effectiveness of gilteritinib(Gilt)-based combination therapy bridging allo-HSCT for FLT3-ITD+R/R AML.Additionally,it aims to assess the impact of Gilt maintenance therapy on the prognosis of patients after allo-HSCT.Methods The clinical data of 26 patients with FLT3-ITD+R/R AML treated at the First Affiliated Hospital of Soochow University from August 2019 to January 2023 were retrospectively analyzed.The analysis included an assessment of the composite complete remission rate(CRc),overall survival(OS)time,disease-free survival(DFS)time,and adverse events experienced by all enrolled patients.Results A total of 26 patients with FLT3-ITD+R/R AML were enrolled,including 14 men and 12 women with a median age of 38(18-65)years.A total of 18 cases were refractory,and eight cases were relapsed.The curative effect evaluation conducted between 14 and 21 days showed that the complete remission(CR)rate was 26.9%(7/26),the CR with hematology incomplete recovery was 57.7%(15/26),and the partial response(PR)rate was 7.7%(2/26).The CRc was 84.6%(22/26),and the minimal residual disease(MRD)negativity rate was 65.4%.The 12 month cumulative OS rate for all patients was 79.0%,and the 24 month cumulative OS rate was 72.0%.The median OS time was not determined.The median follow-up time was 16.0 months.Among the patients who responded to treatment,the 12 month cumulative DFS rate was 78.0%,and the 24 month cumulative DFS rate was 71.0%.The median DFS time was not determined.Patients who received allo-HSCT had a median OS time that was significantly longer than those who did not receive allo-HSCT(3.3 months,95%CI 2.2-4.3 months,P=0.005).The median OS time of patients with or without Gilt maintenance therapy after allo-HSCT was not determined,but the OS time of patients with Gilt maintenance therapy after allo-HSCT treatment was longer than that of patients without Gilt maintenance therapy after allo-HSCT treatment(P=0.019).The FLT3-ITD mutation clearance rate in this study was 38.5%,and the median OS time of patients with FLT3-ITD mutation clearance was not determined but was significantly longer than the median OS of patients without FLT3-ITD mutation clearance(15.0 months;P=0.018).The most common grade 3 and above hematological adverse events of Gilt-based combination therapy included leukopenia(76.9%),neutropenia(76.9%),febrile neutropenia(61.5%),thrombocytopenia(69.2%),and anemia(57.7%).One patient developed differentiation syndrome during oral Gilt maintenance therapy after allo-HSCT treatment,but his condition improved after treatment.Conclusion The Gilt-based combination therapy is highly effective in treating FLT3-ITD+R/R AML.It demonstrates a high CRc,MRD negativity rate,and rapid onset,leading to a significant improvement in patients'survival.Furthermore,the clearance rate of FLT3-ITD mutation is notably high.Additionally,implementing bridging allo-HSCT and Gilt maintenance therapy after allo-HSCT treatment has considerably enhances patients'survival.Closely monitoring and managing any adverse event that may occur during treatment are crucial.

GilteritinibLeukemia,myeloid,acuteRefractoryRelapseFLT3-ITD mutationAllogeneic hematopoietic stem cell transplantation

徐洋、张剑、薛胜利、苗瞄、王荧、陈苏宁、仇惠英、吴德沛

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苏州大学附属第一医院血液内科,江苏省血液研究所,国家血液系统疾病临床医学研究中心,苏州 215006

Gilteritinib 白血病,髓系,急性 难治 复发 FLT3-ITD基因突变 异基因造血干细胞移植

国家重点研发计划国家自然科学基金江苏省血液病医学创新中心项目江苏省自然科学基金江苏省老年健康研究项目

2022YFC250270082020108003CXZX202201BK20201168LKM2023015

2024

中华血液学杂志
中华医学会

中华血液学杂志

CSTPCD北大核心
影响因子:1.17
ISSN:0253-2727
年,卷(期):2024.45(4)