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