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gilteritinib与化疗治疗复发性或难治性FLT3突变型AML的比较
Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML


Alexander E. Perl ... 肿瘤 • 2019.10.31
相关阅读
• gilteritinib治疗FLT3 突变型急性髓系白血病 • 米哚妥林联合化疗治疗FLT3基因突变急性髓系白血病的研究 • FLT3阳性急性髓系白血病的研究进展

摘要


背景

有FMS样酪氨酸激酶3基因(FLT3)突变的复发性或难治性急性髓系白血病(AML)患者很少对挽救性化疗有应答。gilteritinib是一种口服的强效、选择性FLT3抑制剂,单药治疗对复发性或难治性FLT3突变型AML有活性。

 

方法

在一项3期试验中,我们以2∶1的比例将复发性或难治性FLT3突变型AML成人患者随机分组,分别接受gilteritinib(剂量为每日120 mg)或挽救性化疗。两项主要终点是总生存期以及伴有完全或部分血液学恢复的完全缓解的患者百分比。次要终点包括无事件生存期(未发生治疗失败[治疗失败指的是复发或未缓解]并且未死亡)和完全缓解的患者百分比。

 

结果

在371例符合纳入条件的患者中,247例被随机分配至gilteritinib组,124例被随机分配至挽救性化疗组。gilteritinib组的中位总生存期显著超过化疗组(9.3个月vs. 5.6个月;死亡的风险比,0.64;95% CI,0.49~0.83;P<0.001)。gilteritinib组和化疗组的中位无事件生存期分别为2.8个月和0.7个月(治疗失败或死亡的风险比,0.79;95% CI,0.58~1.09)。在gilteritinib组和化疗组中,伴有完全或部分血液学恢复的完全缓解的患者百分比分别为34.0%和15.3%(风险差异,18.6个百分点;95% CI,9.8~27.4);完全缓解的患者百分比分别为21.1%和10.5%(风险差异,10.6个百分点;95% CI,2.8~18.4)。在根据治疗持续时间校正的分析中,gilteritinib组的3级或更高级别不良事件和严重不良事件发生率低于化疗组;在gilteritinib组中,最常见的3级或更高级别不良事件为发热性中性粒细胞减少(45.9%)、贫血(40.7%)和血小板减少(22.8%)。

 

结论

在复发性或难治性FLT3突变型AML患者中,与挽救性化疗相比,gilteritinib显著延长了患者生存期并提高了缓解患者百分比(由安斯泰来制药资助;ADMIRAL在ClinicalTrials.gov注册号为NCT02421939)。





作者信息

Alexander E. Perl, M.D., Giovanni Martinelli, M.D., Jorge E. Cortes, M.D., Andreas Neubauer, M.D., Ellin Berman, M.D., Stefania Paolini, M.D., Ph.D., Pau Montesinos, M.D., Maria R. Baer, M.D., Richard A. Larson, M.D., Celalettin Ustun, M.D., Francesco Fabbiano, M.D., Harry P. Erba, M.D., Ph.D., Antonio Di Stasi, M.D., Robert Stuart, M.D., Rebecca Olin, M.D., Margaret Kasner, M.D., Fabio Ciceri, M.D., Wen-Chien Chou, M.D., Ph.D., Nikolai Podoltsev, M.D., Christian Recher, M.D., Hisayuki Yokoyama, M.D., Naoko Hosono, M.D., Ph.D., Sung-Soo Yoon, M.D., Ph.D., Je-Hwan Lee, M.D., Ph.D., Timothy Pardee, M.D., Ph.D., Amir T. Fathi, M.D., Chaofeng Liu, Ph.D., Nahla Hasabou, M.D., Xuan Liu, Ph.D., Erkut Bahceci, M.D., and Mark J. Levis, M.D., Ph.D.
From the Abramson Cancer Center, University of Pennsylvania (A.E.P.), and Thomas Jefferson University (M.K.) — both in Philadelphia; Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Istituto Di Ricovero e Cura a Carattere Scientifico (IRCCS), Meldola (G.M.), L. and A. Seràgnoli Institute of Hematology, Bologna University Medical School, Bologna (S.P.), Ospedali Riuniti Villa Sofia-Cervello, Palermo (F.F.), and IRCCS San Raffaele Scientific Institute, Milan (F.C.) — all in Italy; University of Texas M.D. Anderson Cancer Center, Houston (J.E.C.); Universitätsklinikum Giessen und Marburg, Marburg, Germany (A.N.); Memorial Sloan Kettering Cancer Center, New York (E. Berman); Hospital Universitari i Politècnic La Fe, Valencia, and Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto Carlos III, Madrid — both in Spain (P.M.); University of Maryland Greenebaum Comprehensive Cancer Center (M.R.B.) and Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University (M.J.L.) — both in Baltimore; University of Chicago, Chicago (R.A.L.), and Astellas Pharma, Northbrook (C.L., N. Hasabou, X.L., E. Bahceci) — both in Illinois; University of Minnesota, Minneapolis (C.U.); University of Alabama at Birmingham, Birmingham (H.P.E., A.D.S.); Hollings Cancer Center, Medical University of South Carolina, Charleston (R.S.); University of California, San Francisco, San Francisco (R.O.); National Taiwan University, Taipei City, Taiwan (W.-C.C.); Yale University School of Medicine, New Haven, CT (N.P.); Centre Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse Oncopole, Université Toulouse III Paul Sabatier, Toulouse, France (C.R.); Sendai Medical Center, National Hospital Organization, Sendai (H.Y.), and University of Fukui, Fukui (N. Hosono) — both in Japan; Seoul National University (S.-S.Y.) and Asan Medical Center, University of Ulsan College of Medicine (J.-H.L.) — both in Seoul, South Korea; Wake Forest Baptist Medical Center, Winston-Salem, NC (T.P.); and Massachusetts General Hospital, Harvard Medical School, Boston (A.T.F.). Address reprint requests to Dr. Perl at the Perelman Center for Advanced Medicine 12 South, 3400 Civic Center Blvd., Philadelphia, PA 19104, or at alexander.perl@uphs.upenn.edu.

 

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