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利妥昔单抗治疗儿童高危成熟B细胞非霍奇金淋巴瘤
Rituximab for High-Risk, Mature B-Cell Non-Hodgkin’s Lymphoma in Children


Véronique Minard-Colin ... 肿瘤 妇产科和儿科 • 2020.06.04
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摘要


背景

化疗加用利妥昔单抗可延长成人B细胞癌患者的生存期,但在儿童高级别成熟B细胞非霍奇金淋巴瘤患者中的疗效和安全性数据有限。

 

方法

我们在<18岁的高危成熟B细胞非霍奇金淋巴瘤(乳酸脱氢酶水平升高的Ⅲ期淋巴瘤或Ⅳ期淋巴瘤)或急性白血病患者中开展了一项开放标签的3期国际性随机试验,试验中比较了标准LMB(lymphomes malins B)化疗加用6剂利妥昔单抗治疗和单独标准LMB化疗。主要终点是无事件生存期。研究还评估了总生存期和毒性作用。

 

结果

分析是基于被随机分组的328例患者(每组164例患者),85.7%的患者患伯基特淋巴瘤。中位随访期为39.9个月。本研究观察到利妥昔单抗-化疗组10例患者和化疗组28例患者发生了事件。在利妥昔单抗-化疗组和化疗组中,3年时的无事件生存率分别为93.9%(95%置信区间[CI],89.1~96.7)和82.3%(95% CI,75.7~87.5)(原发性难治性疾病或首次发生进展、缓解后复发、全因死亡或第二癌症的风险比,0.32;95% CI,0.15~0.66;单侧P=0.00096,达到了这一分析要求的显著性水平)。利妥昔单抗-化疗组8例患者(4例死亡与疾病相关,3例与治疗不相关,1例死于第二癌症)和化疗组20例患者死亡(17例死亡与疾病相关,3例与治疗相关)(风险比,0.36;95% CI,0.16~0.82)。在利妥昔单抗-化疗组和化疗组中,细胞减积期治疗(prephase treatment)后4级或更高级别急性不良事件的发生率分别为33.3%和24.2%(P=0.07);事件主要与发热性中性粒细胞减少和感染有关。纳入试验后1年时,利妥昔单抗-化疗组IgG水平低的患者人数约为化疗组的2倍。

 

结论

在儿童和青少年高级别、高危成熟B细胞非霍奇金淋巴瘤患者中,标准LMB化疗加用利妥昔单抗显著延长了无事件生存期和总生存期,并且与较高的低丙种球蛋白血症发生率和可能较多的感染相关(由法国卫生部临床研究医院计划[Clinical Research Hospital Program]等资助,在ClinicalTrials.gov注册号为NCT01516580)。





作者信息

Véronique Minard-Colin, M.D., Ph.D., Anne Aupérin, M.D., Ph.D., Marta Pillon, M.D., Ph.D., G.A. Amos Burke, M.B., Ch.B., Ph.D., Donald A. Barkauskas, Ph.D., Keith Wheatley, Ph.D., Rafael F. Delgado, M.D., Ph.D., Sarah Alexander, M.D., Anne Uyttebroeck, M.D., Ph.D., Catherine M. Bollard, M.D., Ph.D., József Zsiros, M.D., Ph.D., Monika Csoka, M.D., Ph.D., Bernarda Kazanowska, M.D., Ph.D., Alan K. Chiang, M.D., Ph.D., Rodney R. Miles, M.D., Ph.D., Andrew Wotherspoon, M.D., Ph.D., Peter C. Adamson, M.D., Ph.D., Gilles Vassal, M.D., Ph.D., Catherine Patte, M.D., and Thomas G. Gross, M.D., Ph.D. for the European Intergroup for Childhood Non-Hodgkin Lymphoma, and the Children’s Oncology Group*
From the Departments of Pediatric and Adolescent Oncology (V.M.-C., C.P.) and Clinical Research (G.V.), INSERM Unité 1015 (V.M.-C.), and the Unit of Biostatistics and Epidemiology and INSERM Unité 1018 (A.A.), Gustave Roussy, Université Paris-Saclay, Villejuif, France; the Department of Pediatric Hematology and Oncology, University of Padua, Padua, Italy (M.P.); the Department of Paediatric Haematology, Oncology, and Palliative Care, Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Cambridge (G.A.A.B.), Cancer Research UK Clinical Trials Unit, Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham, Birmingham (K.W.), and the Department of Histopathology, Royal Marsden NHS Foundation Trust, London (A.W.) — all in the United Kingdom; the Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles (D.A.B.); the Department of Pediatric Hematology and Oncology, University of Valencia, Valencia, Spain (R.F.D.); the Division of Haematology–Oncology, Hospital for Sick Children, Toronto (S.A.); the Department of Pediatric Hematology and Oncology, University Hospitals Leuven, Leuven, Belgium (A.U.); the Center for Cancer and Immunology Research, Children’s National Health System and George Washington University, Washington, DC (C.M.B.); Princess Máxima Center for Pediatric Oncology, Utrecht, the Netherlands (J.Z.); the Department of Pediatric Hematology and Oncology, Semmelweis University, Budapest, Hungary (M.C.); the Department of Pediatric Bone Marrow Transplantation, Oncology, and Hematology, Wroclaw Medical University, Wroclaw, Poland (B.K.); the Department of Pediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong (A.K.C.); the Department of Pathology, University of Utah, Salt Lake City (R.R.M.); Children’s Hospital of Philadelphia, Philadelphia (P.C.A.); and the National Cancer Institute, Center for Global Health, Rockville, MD (T.G.G.). Address reprint requests to Dr. Minard-Colin at Gustave Roussy, 114 Rue Edouard Vaillant, Villejuif 94805, France, or at veronique.minard@gustaveroussy.fr. *A complete list of the investigators in the European Intergroup for Childhood Non-Hodgkin Lymphoma and the Children’s Oncology Group is provided in the Supplementary Appendix, available at NEJM.org.

 

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