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利妥昔单抗+化疗治疗儿童高危成熟B细胞非霍奇金淋巴瘤疗效显著
作者:小柯机器人 发布时间:2020/6/5 15:46:02

法国古斯塔夫·鲁西研究所Véronique Minard-Colin团队探讨了利妥昔单抗治疗儿童高危成熟B细胞非霍奇金淋巴瘤的效果。该成果发表在2020年6月4日出版的《新英格兰医学杂志》上。

利妥昔单抗+化疗中可延长B细胞肿瘤成人患者的生存期。但其对高级别、成熟B细胞非霍奇金淋巴瘤儿童患者的疗效和安全性数据有限。

研究组进行了一项开放标签、国际、随机、3期临床试验,招募了328例18岁以下、高危、成熟B细胞非霍奇金淋巴瘤(III级伴乳酸脱氢酶水平升高或IV级)或急性白血病患者,85.7%患有伯基特氏淋巴瘤。将其随机分组,其中164例接受标准淋巴瘤马林斯B(LMB)化疗,164例接受标准LMB化疗+利妥昔单抗。 

中位随访39.9个月后,利妥昔单抗+化疗组中有10例患者发生了疾病进展、复发、全因死亡、二次癌症等事件,化疗组中有28例。利妥昔单抗+化疗组的3年无事件生存率为93.9%,显著高于化疗组(82.3%)。利妥昔单抗+化疗组中有8例患者死亡(4例与疾病相关,3例与治疗相关,1例与二次癌症相关),化疗组中有20例(17例与疾病相关,3例与治疗相关)。在前期治疗后,利妥昔单抗+化疗组中4级及以上急性不良事件发生率为33.3%,化疗组为24.2%,事件主要与发热性中性粒细胞减少和感染有关。纳入试验1年后,利妥昔单抗+化疗组低IgG水平的患者约为化疗组的两倍。

总之,标准LMB化疗+利妥昔单抗可显著延长儿童和青少年高级别、高危、成熟B细胞非霍奇金淋巴瘤的无事件生存期和总生存期,但与低丙种球蛋白血症的高发病率和潜在的更多感染发作相关。

附:英文原文

Title: Rituximab for High-Risk, Mature B-Cell Non-Hodgkin’s Lymphoma in Children

Author: 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.

Issue&Volume: 2020-06-03

Abstract: Abstract

Background

Rituximab added to chemotherapy prolongs survival among adults with B-cell cancer. Data on its efficacy and safety in children with high-grade, mature B-cell non-Hodgkin’s lymphoma are limited.

Methods

We conducted an open-label, international, randomized, phase 3 trial involving patients younger than 18 years of age with high-risk, mature B-cell non-Hodgkin’s lymphoma (stage III with an elevated lactate dehydrogenase level or stage IV) or acute leukemia to compare the addition of six doses of rituximab to standard lymphomes malins B (LMB) chemotherapy with standard LMB chemotherapy alone. The primary end point was event-free survival. Overall survival and toxic effects were also assessed.

Results

Analyses were based on 328 patients who underwent randomization (164 patients per group); 85.7% of the patients had Burkitt’s lymphoma. The median follow-up was 39.9 months. Events were observed in 10 patients in the rituximab–chemotherapy group and in 28 in the chemotherapy group. Event-free survival at 3 years was 93.9% (95% confidence interval [CI], 89.1 to 96.7) in the rituximab–chemotherapy group and 82.3% (95% CI, 75.7 to 87.5) in the chemotherapy group (hazard ratio for primary refractory disease or first occurrence of progression, relapse after response, death from any cause, or second cancer, 0.32; 95% CI, 0.15 to 0.66; one-sided P=0.00096, which reached the significance level required for this analysis). Eight patients in the rituximab–chemotherapy group died (4 deaths were disease-related, 3 were treatment-related, and 1 was from a second cancer), as did 20 in the chemotherapy group (17 deaths were disease-related, and 3 were treatment-related) (hazard ratio, 0.36; 95% CI, 0.16 to 0.82). The incidence of acute adverse events of grade 4 or higher after prephase treatment was 33.3% in the rituximab–chemotherapy group and 24.2% in the chemotherapy group (P=0.07); events were related mainly to febrile neutropenia and infection. Approximately twice as many patients in the rituximab–chemotherapy group as in the chemotherapy group had a low IgG level 1 year after trial inclusion.

Conclusions

Rituximab added to standard LMB chemotherapy markedly prolonged event-free survival and overall survival among children and adolescents with high-grade, high-risk, mature B-cell non-Hodgkin’s lymphoma and was associated with a higher incidence of hypogammaglobulinemia and, potentially, more episodes of infection.

DOI: 10.1056/NEJMoa1915315

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1915315

期刊信息

The New England Journal of Medicine:《新英格兰医学杂志》,创刊于1812年。隶属于美国麻省医学协会,最新IF:70.67
官方网址:http://www.nejm.org/
投稿链接:http://www.nejm.org/page/author-center/home