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维奈托克联合奥比妥珠单抗治疗有合并症的CLL患者
Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions


Kirsten Fischer ... 肿瘤 • 2019.06.06
相关阅读
• Venetoclax靶向BCL2治疗复发性慢性淋巴细胞白血病

两项NEJM发表的研究,将打开慢性淋巴细胞白血病临床治愈之门

 

王建祥†*,杨大俊‡

†中国医学科学院血液学研究所;‡中山大学肿瘤防治中心

*通讯作者

 

2019年5月30日和6月6日,《新英格兰医学杂志》(NEJM)连续两期刊登关于维奈托克(venetoclax)联合用药治疗慢性淋巴细胞白血病的论著1,2。其中,维奈托克(venetoclax)联合奥比妥珠单抗(obinutuzumab)一线治疗有合并症的CLL患者研究(CLL14)在本周结束的ASCO 2019年会上发布。因为其优异的疗效,FDA已在今年5月批准这一疗法。

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摘要


背景

BCL2抑制剂维奈托克(venetoclax)已经对慢性淋巴细胞白血病(CLL)患者表现出活性,但维奈托克联合其他药物治疗有合并症的CLL患者的疗效尚不清楚。

 

方法

在这项开放标签的3期试验中,我们在未经治、有合并症的CLL患者中研究了固定疗程的维奈托克联合奥比妥珠单抗治疗。疾病累计评分表(Cumulative Illness Rating Scale,评分范围为0~56分,较高评分表示器官系统功能受损较严重)评分大于6分或肌酐清除率计算值小于70 mL/min的患者被随机分组,分别接受维奈托克-奥比妥珠单抗或苯丁酸氮芥-奥比妥珠单抗治疗。主要终点是研究者判定的无进展生存期。我们还评价了各治疗方案的安全性。

 

结果

共有432例患者(中位年龄,72岁;中位疾病累计评分表评分,8分;中位肌酐清除率,66.4 mL/min)被随机分组,每组各216例患者。中位随访28.1个月后,维奈托克-奥比妥珠单抗组和苯丁酸氮芥-奥比妥珠单抗组分别发生了30起和77起主要终点事件(疾病进展或死亡)(风险比,0.35;95%置信区间[CI],0.23~0.53;P<0.001)。维奈托克-奥比妥珠单抗组24个月时无进展生存率的Kaplan-Meier估计值显著高于苯丁酸氮芥-奥比妥珠单抗组:分别为88.2%(95% CI,83.7~92.6)和64.1%(95% CI,57.4~70.8)。这一获益也见于有TP53缺失、突变或两者同时存在的患者,以及免疫球蛋白重链基因无突变的患者。在维奈托克-奥比妥珠单抗组和苯丁酸氮芥-奥比妥珠单抗组中,3级或4级中性粒细胞减少的发生率分别为52.8%和48.1%,3级或4级感染的发生率分别为17.5%和15.0%。维奈托克-奥比妥珠单抗组和苯丁酸氮芥-奥比妥珠单抗组的全因死亡率分别为9.3%和7.9%。这些差异不显著。

 

结论

在未经治的有合并症CLL患者中,维奈托克-奥比妥珠单抗组的无进展生存期超过苯丁酸氮芥-奥比妥珠单抗组(由罗氏制药和艾伯维资助;在ClinicalTrials.gov注册号为NCT02242942)。





作者信息

Kirsten Fischer, M.D., Othman Al-Sawaf, M.D., Jasmin Bahlo, Ph.D., Anna-Maria Fink, M.D., Maneesh Tandon, M.D., Mark Dixon, M.Sc., Sandra Robrecht, Ph.D., Simon Warburton, M.Sc., Kathryn Humphrey, B.Sc., Olga Samoylova, M.D., Anna M. Liberati, M.D., Javier Pinilla-Ibarz, M.D., Ph.D., Stephen Opat, M.D., Liliya Sivcheva, M.D., Katell Le Dû, M.D., Laura M. Fogliatto, M.D., Carsten U. Niemann, M.D., Ph.D., Robert Weinkove, M.D., Sue Robinson, M.D., Thomas J. Kipps, M.D., Ph.D., Sebastian Boettcher, M.D., Eugen Tausch, M.D., Rod Humerickhouse, M.D., Barbara Eichhorst, M.D., Clemens-Martin Wendtner, M.D., Anton W. Langerak, Ph.D., Karl-Anton Kreuzer, M.D., Matthias Ritgen, M.D., Valentin Goede, M.D., Stephan Stilgenbauer, M.D., Mehrdad Mobasher, M.D., M.P.H., and Michael Hallek, M.D.
From Department I of Internal Medicine, Center for Integrated Oncology Aachen–Bonn–Cologne–Duesseldorf, University Hospital Cologne and University of Cologne (K.F., O.A.-S., J.B., A.-M.F., S. Robrecht, B.E., K.-A.K., M.H.), the Oncogeriatric Unit, Department of Geriatric Medicine, St. Marien Hospital (V.G.), CECAD (Center of Excellence on Cellular Stress Responses in Aging-Associated Diseases) (M.H.), Center for Molecular Medicine Cologne (M.H.), Cologne, Department III of Internal Medicine, University Hospital Rostock, Rostock (S.B.), Department III of Internal Medicine, Ulm University, Ulm (E.T., S.S.), the Departments of Hematology, Oncology, Immunology, Palliative Care, Infectious Diseases, and Tropical Medicine, Klinikum Schwabing, Munich (C.-M.W.), Department II of Internal Medicine, Campus Kiel, University of Schleswig-Holstein, Kiel (M.R.), and the Department of Hematology, Oncology, and Rheumatology, Saarland University Medical School, Homburg (S.S.) — all in Germany; Roche Products, Welwyn Garden City, United Kingdom (M.T., M.D., S.W., K.H.); Regional Clinical Hospital N.A. Semashko, Nizhny Novgorod, Russia (O.S.); the Division of Onco-Hematology, Santa Maria Terni Hospital, University of Perugia, Perugia, Italy (A.M.L.); the Department of Malignant Hematology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL (J.P.-I.); the Haematology Department, School of Clinical Sciences at Monash Health, Monash University, Clayton, VIC, Australia (S.O.); First Internal Department, Multiprofile Hospital for Active Treatment Hristo Botev, Vratsa, Bulgaria (L.S.); the Hematology Department, Clinique Victor Hugo, Le Mans, France (K.L.D.); Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil (L.M.F.); the Department of Hematology, Rigshospitalet, Copenhagen University Hospital, Copenhagen (C.U.N.); Wellington Blood and Cancer Centre, Capital and Coast District Health Board, and Malaghan Institute of Medical Research, Wellington, New Zealand (R.W.); Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada (S. Robinson); Moores Cancer Center, University of California San Diego, San Diego (T.J.K.), and Genentech, South San Francisco (M.M.) — both in California; AbbVie, North Chicago, IL (R.H.); and the Department of Immunology, Laboratory Medical Immunology, Erasmus MC, Rotterdam, the Netherlands (A.W.L.). Address reprint requests to Dr. Hallek at Department I of Internal Medicine, Center of Integrated Oncology Cologne Bonn, University Hospital of Cologne, Kerpener Str. 62, 50937 Cologne, Germany, or at michael.hallek@uni-koeln.de.

 

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