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博纳吐单抗和化疗在进展期急性淋巴细胞白血病治疗中的比较研究
Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia


Hagop Kantarjian ... 肿瘤 • 2017.03.02
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免疫治疗在复发/难治性急性淋巴细胞白血病中大放异彩

 

张敏

华中科技大学同济医学院附属协和医院血液病研究所

 

成人急性B淋巴细胞白血病(B-ALL,简称急淋)的复发是目前的难题,而采用标准的挽救性方案缓解率(CR)仅18%~44%,且缓解持续时间非常短暂1,2。近年来,免疫治疗在急淋的治疗中越来越受到重视3,4。博纳吐单抗是一种双特异性的T细胞衔接抗体,它可以同时连接CD3+的细胞毒T细胞和CD19+的B细胞,从而使内源性T细胞能够识别并且消灭CD19+的ALL细胞。

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摘要


背景

博纳吐单抗是一种能使CD3+ T细胞识别和清除CD19+急性淋巴细胞白血病(ALL)原始细胞的双特异性单抗构建体。基于其在单组试验中显示出的疗效和可控的毒性作用,博纳吐单抗获得批准用于复发性或难治性前体B细胞ALL的治疗。

 

方法

在本项多机构3期临床试验中,我们将接受过大量治疗的前体B细胞ALL成人患者按照2∶1的比例随机分组进行博纳吐单抗或标准化疗。主要终点是总生存期。

 

结果

在被随机分配接受博纳吐单抗(271例患者)或化疗(134例患者)的405例患者中,376例患者接受了至少一剂药治疗。博纳吐单抗组的总生存期显著长于化疗组。博纳吐单抗组的中位总生存期为7.7个月而化疗组为4.0个月(博纳吐单抗组与化疗组相比的死亡风险比为0.71;95%置信区间[CI]为0.55~0.93;P=0.01)。博纳吐单抗组的治疗开始后12周内的缓解率显著高于化疗组,不论是具有完全血液学恢复的完全缓解(34%对16%,P<0.001),还是具有完全、部分或不完全血液学恢复的完全缓解(44%对25%,P<0.001)。与化疗相比,博纳吐单抗治疗可提高无事件生存率(6个月估算,31%对12%;达到具有完全、部分或不完全血液学恢复的完全缓解后发生复发事件或者死亡的风险比为0.55;95% CI,0.43~0.71;P<0.001),同时可延长中位缓解持续时间(7.3对4.6个月)。各组中共计24%的患者接受了异体干细胞移植。据报道,博纳吐单抗组87%的患者和化疗组92%的患者发生了≥3级的不良事件。

 

结论

与化疗相比,博纳吐单抗治疗可显著延长复发性或难治性前体B细胞ALL成人患者的总生存期(由安进[Amgen]公司资助;TOWER在ClinicalTrials.gov注册号为NCT02013167)。





作者信息

Hagop Kantarjian, M.D., Anthony Stein, M.D., Nicola Gökbuget, M.D., Adele K. Fielding, M.B., B.S., Ph.D., Andre C. Schuh, M.D., Josep-Maria Ribera, M.D., Ph.D., Andrew Wei, M.B., B.S., Ph.D., Hervé Dombret, M.D., Robin Foà, M.D., Renato Bassan, M.D., Önder Arslan, M.D., Miguel A. Sanz, M.D., Ph.D., Julie Bergeron, M.D., Fatih Demirkan, M.D., Ewa Lech-Maranda, M.D., Ph.D., Alessandro Rambaldi, M.D., Xavier Thomas, M.D., Ph.D., Heinz-August Horst, M.D., Ph.D., Monika Brüggemann, M.D., Wolfram Klapper, M.D., Ph.D., Brent L. Wood, M.D., Ph.D., Alex Fleishman, M.S., Dirk Nagorsen, M.D., Ph.D., Christopher Holland, M.S., Zachary Zimmerman, M.D., Ph.D., and Max S. Topp, M.D.
From the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston (H.K.); City of Hope National Medical Center, Duarte (A.S.), and Amgen, Thousand Oaks (A.F., D.N., Z.Z.) — both in California; Goethe University, University Hospital, Department of Medicine II, Frankfurt am Main (N.G.), Medical Department II (H.-A.H., M.B.) and Hematopathology Section and Lymph Node Registry (W.K.), University Hospital Schleswig Holstein, Campus Kiel, Kiel, and Medizinische Klinik und Poliklinik II, Universitätsklinikums Würzburg, Würzburg (M.S.T.) — all in Germany; Royal Free Hospital and University College London Cancer Institute, London (A.K.F.); Princess Margaret Cancer Centre, Toronto (A.C.S.), and Centre Intégré Universitaire de Santé et de Services Sociaux de l’est de l’île de Montréal, Hôpital Maisonneuve-Rosemont, Montreal (J.B.) — all in Canada; ICO-Hospital Universitari Germans Trias i Pujol, Jose Carreras Research Institute, Universitat Autonoma de Barcelona, Barcelona (J.-M.R.), the Department of Medicine, Hospital Universitari i Politecnic La Fe, University of Valencia, Valencia, and Centro de Investigación Biomédica en Red de Cáncer, Instituto Carlos III, Madrid (M.A.S.) — all in Spain; Alfred Hospital and Monash University, Melbourne, VIC, Australia (A.W.); Institut Universitaire d’Hématologie, Hôpital Saint-Louis (Assistance Publique – Hôpitaux de Paris), Paris (H.D.), and Centre Hospitalier Lyon Sud, Pierre-Benite (X.T.) — both in France; Ematologia, Dipartimento di Biotecnologie Cellulari ed Ematologia, Azienda Ospedaliera Policlinico Umberto I, Università Sapienza di Roma, Rome (R.F.), Azienda Unità Locale Socio Sanitaria 12 Veneziana Ospedale Dell Angelo, Venice (R.B.), and Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Università Statale di Milano, Milan (A.R.) — all in Italy; Ankara Universitesi, Tip Fakültesi, Cebeci Arastirma ve Uygulama Hastanesi, Ankara (Ö.A.), and Dokuz Eylül Üniversitesi Tıp Fakültesi, İzmir (F.D.) — both in Turkey; Instytut Hematologii i Transfuzjologii and Centrum Medyczne Kształcenia Podyplomowego, Warsaw, Poland (E.L.-M.); University of Washington Medical Center, Seattle (B.L.W.); and Amgen, Washington, DC (C.H.). Address reprint requests to Dr. Kantarjian at the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, or at hkantarjian@mdanderson.org.

 

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