在 newly diagnosed FLT3-ITD AML 患者中，ALLG 进行了一项随机、安慰剂对照的研究，研究对象接受索拉非尼联合强化化疗的治疗方案。
Sorafenib plus intensive chemotherapy in newly diagnosed FLT3-ITD AML:a randomized, placebo-controlled study by the ALLG.
发表日期：2023 Aug 30
作者：
Sun Loo, Andrew W Roberts, Natasha S Anstee, Glen A Kennedy, Simon Zhao-Xiong He, Anthony P Schwarer, Anoop Kumar Enjeti, James D'Rozario, Paula Marlton, Ian Bilmon, John M Taper, Gavin Cull, Campbell Tiley, Emma Verner, Uwe Hahn, Devendra K Hiwase, Harry J Iland, Nicholas Edward Murphy, Sundra Ramanathan, John Reynolds, Doen Ming Ong, Ing Soo Tiong, Meaghan Wall, Michael Murray, Tristan Rawling, Joanna Leadbetter, Leesa Rowley, Maya Latimer, Sam L S Yuen, Stephen B Ting, Chun Yew Fong, Kirk Lachlan Morris, Ashish Bajel, John F Seymour, Mark J Levis, Andrew H Wei
来源：
BLOOD
摘要：
索拉非尼维持治疗改善了FLT3-ITD急性髓系白血病（AML）造血干细胞移植（HCT）后患者的预后。尽管索拉非尼维持治疗与强化化疗的联合使用取得了有希望的结果，但随机数据有限。该安慰剂对照的2期研究（ACTRN12611001112954）随机分为2组（2:1），将102名年龄在18-65岁之间的患者分别接受索拉非尼维持治疗或安慰剂治疗（第4-10天），并结合强化诱导治疗；伊达比星12mg/m2，第1-3天，阿糖胞苷1.5g/m2，第1、3、5、7天两次每日（18-55岁），或者100mg/m2，第1-7天（56-65岁），巩固治疗，继而在新诊断的FLT3-ITD AML患者中进行为期12个月（骨髓移植后除外）的维持治疗。在修正意向治疗最终分析中，有4名患者被排除（3名未接受剂量，1名后续发现FLT3-ITD阴性）。完全缓解（CR）/ CR伴不完全造血恢复（CRi）的率在两组中均较高（索拉非尼治疗组78%/9%，安慰剂组70%/24%）。根据49.1个月的中位随访，索拉非尼并未改善主要终点事件无效生存（EFS）（2年EFS为47.9% vs 45.4%）（危险比[HR] 0.87；95%置信区间[CI]为0.51-1.51，p=0.61）。索拉非尼治疗组的2年总生存率（OS）为67%，安慰剂组为58%（HR为0.76；95% CI为0.42-1.39）。对于在第一缓解期行移植的患者，索拉非尼组和安慰剂组的2年OS分别为84%和67%（HR为0.45；95% CI为0.18-1.12，p=0.08）。在探索性分析中，诱导治疗后FLT3-ITD可测残留病变阴性状态（<0.001%）与改善的2年OS相关（83% vs 60%）（HR为0.4；95% CI为0.17-0.93，p=0.028）。总的来说，本研究不支持在未选择的FLT3-ITD AML患者中常规使用移植前索拉非尼联合化疗的观点。Copyright © 2023 American Society of Hematology.
Sorafenib maintenance improves outcome after hematopoietic cell transplant (HCT) for patients with FLT3-ITD acute myeloid leukemia (AML). Although promising outcomes have been reported for sorafenib plus intensive chemotherapy, randomized data are limited. This placebo-controlled, phase 2 study (ACTRN12611001112954) randomized 102 patients 18-65 years (2:1) to sorafenib vs placebo (days 4-10) combined with intensive induction; idarubicin 12mg/m2 days 1-3 plus cytarabine 1.5g/m2 twice daily on days 1,3,5,7 (18-55 years) or 100mg/m2 days 1-7 (56-65 years), consolidation therapy, followed by maintenance treatment for 12 months (post-HCT excluded) in newly diagnosed FLT3-ITD AML. Four patients were excluded from modified intention-to-treat final analysis (3 not dosed and 1 later found to be FLT3-ITD negative). Rates of complete remission (CR)/CR with incomplete hematologic recovery (CR/CRi) were high in both arms (sorafenib 78%/9%, placebo 70%/24%). With 49.1 months median follow-up, the primary endpoint of event-free survival (EFS) was not improved by sorafenib (2-year EFS 47.9% vs 45.4%)(hazard ratio [HR] 0.87;95% confidence interval [CI] 0.51-1.51, p=0.61). Two-year overall survival (OS) was 67% in the sorafenib arm and 58% in the placebo arm (HR 0.76; 95% CI 0.42-1.39). For patients transplanted in first remission, 2-year OS was 84% and 67% in the sorafenib and placebo arms, respectively (HR 0.45;95% CI 0.18-1.12, p=0.08). In exploratory analyses, FLT3-ITD measurable residual disease negative status (<0.001%) post-induction was associated with improved 2-year OS (83% vs 60%) (HR 0.4;95% CI 0.17-0.93, p=0.028). In conclusion, routine use of pre-transplant sorafenib plus chemotherapy in unselected patients with FLT3-ITD AML is not supported by this study.Copyright © 2023 American Society of Hematology.