Tedjaseputra Aditya, Tey Amanda, Nalpantidis Anastasios, Grigoriadis George, Fleming Shaun, Vilcassim Shahla, Fedele Pasquale L, Low Michael Sze Yuan, Yeh Paul, Gilbertson Michael, Bennett Ashwini, Gregory Gareth P, Oh Danielle, Gairns Donna, Kaplan Zane, Chunilal Sanjeev D, Brown Susan, Opat Stephen, Chua Chong C, Shortt Jake
Monash Haematology, Monash Health, Melbourne, Victoria, Australia.
Department of Haematology, Guy's and St. Thomas' NHS Foundation Trust, London, UK.
Intern Med J. 2025 May;55(5):749-759. doi: 10.1111/imj.70010. Epub 2025 Mar 7.
After pharmaceutical benefits scheme approval of midostaurin for fms-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukaemia (AML) in 2018, the Australasian Leukaemia & Lymphoma Group (ALLG) proposed a consensus approach to AML induction with 7+3 chemotherapy (7 days of infusional cytarabine with three doses of anthracycline) to align with future clinical trial protocols.
To determine the efficacy and safety of idarubicin-based 7+3 induction ± midostaurin (per ALLG recommendations) in a real-world, tertiary hospital setting.
Data were prospectively collected for all patients assessed for front-line AML treatment. Disease risk and response assessments were defined by European LeukaemiaNet 2017 guidelines. Efficacy and safety endpoints included complete remission (CR) rates, composite CR rates, event-free survival (EFS), overall survival (OS), induction mortality, duration of cytopenias and intensive care unit (ICU) utilisation. Analysis was planned following completion of ≥50 inductions and 5-year aggregated experience.
Between 2018 and 2023, 58 patients (median age 49 years) received 7+3 induction with CR and induction mortality rates of 88% (95% confidence interval (95% CI): 77-95%) and 1.7% (95% CI: 0-9%) respectively. At a median of 24.6 months of follow-up, median OS was 17.6 months for adverse-risk versus not reached for non-adverse-risk patients (P = 0.03). FLT3-mutated patients demonstrated an 89% CR rate (95% CI: 67%-99%) with comparable 4-year EFS (65%) and OS (68%) to FLT3-wild-type patients. Safety across 58 induction and 139 consolidation cycles was acceptable, with a single death and a 21% ICU admission rate (95% CI: 11%-33%) during induction.
Idarubicin-based 7+3 induction with contemporary supportive care yields good safety and CR rates, including in midostaurin-treated FLT3-mutated patients. Survival outcomes for adverse-risk AML patients remain suboptimal.
2018年米哚妥林获药品福利计划批准用于治疗伴有FMS样酪氨酸激酶3（FLT3）突变的急性髓系白血病（AML）后，澳大拉西亚白血病与淋巴瘤组（ALLG）提出了一种采用7+3化疗方案（7天持续静脉滴注阿糖胞苷加三剂蒽环类药物）进行AML诱导治疗的共识方法，以与未来的临床试验方案保持一致。
在一家三级医院的实际环境中，确定基于伊达比星的7+3诱导化疗联合米哚妥林（按照ALLG的建议）的疗效和安全性。
前瞻性收集所有接受一线AML治疗评估患者的数据。疾病风险和缓解评估按照欧洲白血病网络2017年指南进行定义。疗效和安全性终点包括完全缓解（CR）率、复合CR率、无事件生存期（EFS）、总生存期（OS）、诱导死亡率、血细胞减少持续时间和重症监护病房（ICU）使用率。计划在完成≥50次诱导化疗和5年汇总经验后进行分析。
2018年至2023年期间，58例患者（中位年龄49岁）接受了7+3诱导化疗，CR率和诱导死亡率分别为88%（95%置信区间（95%CI）：77%-95%）和1.7%（95%CI：0%-9%）。在中位随访24.6个月时，高危患者的中位OS为17.6个月，而低危患者未达到（P=0.03）。FLT3突变患者的CR率为89%（95%CI：67%-99%），4年EFS（65%）和OS（68%）与FLT3野生型患者相当。58个诱导化疗周期和139个巩固化疗周期的安全性是可接受的，诱导化疗期间有1例死亡，ICU入住率为21%（95%CI：11%-33%）。
基于伊达比星的7+3诱导化疗联合当代支持治疗具有良好的安全性和CR率，包括在接受米哚妥林治疗的FLT3突变患者中。高危AML患者的生存结局仍然不理想。
