Rituximab for High-Risk, Mature B-Cell Non-Hodgkin's Lymphoma in Children.
Rituximab for High-Risk, Mature B-Cell Non-Hodgkin's Lymphoma in Children.
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DOI：
10.1056/nejmoa1915315
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发表时间：
2020-06-04
期刊：
影响因子：
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通讯作者：
Children’s Oncology Group
中科院分区：
文献类型：
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作者：
Minard-Colin V;Aupérin A;Pillon M;Burke GAA;Barkauskas DA;Wheatley K;Delgado RF;Alexander S;Uyttebroeck A;Bollard CM;Zsiros J;Csoka M;Kazanowska B;Chiang AK;Miles RR;Wotherspoon A;Adamson PC;Vassal G;Patte C;Gross TG;European Intergroup for Childhood Non-Hodgkin Lymphoma;Children’s Oncology Group
利妥昔单抗加化疗可提高成人B细胞癌患者的生存率关于其在儿童高级别、成熟B细胞非霍奇金淋巴瘤中的疗效和安全性的数据有限。我们进行了一项开放标签、国际性、随机、3期临床试验，纳入了18岁以下的高危、成熟B细胞非霍奇金淋巴瘤（III期伴乳酸脱氢酶水平升高或IV期）或急性白血病患者，以比较6剂利妥昔单抗加标准淋巴瘤马林B（LMB）化疗与标准LMB化疗单独治疗。主要终点是无事件生存。还评估了总生存期和毒性作用。分析基于328例接受随机分组的患者（每组164例患者）; 85.7%的患者患有伯基特淋巴瘤。中位随访时间为39.9个月。在利妥昔单抗化疗组的10名患者和化疗组的28名患者中观察到事件。3年无事件生存率为93.9%（95%置信区间[CI]，89.1至96.7），利妥昔单抗化疗组为82.3%，化疗组（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、任何原因导致的死亡或继发性癌症的风险比为0.32; 95% CI，0.15 - 0.66;单侧P = 0.00096，达到本分析所需的显著性水平）。利妥昔单抗化疗组有8例患者死亡（4例死亡与疾病相关，3例与治疗相关，1例来自第二种癌症），化疗组有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至0.82）。前期治疗后4级或以上急性不良事件的发生率在利妥昔单抗化疗组为33.3%，在化疗组为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。试验入选后1年，利妥昔单抗化疗组中IgG水平较低的患者约为化疗组的两倍。标准LMB化疗加用利妥昔单抗可显著延长儿童和青少年高级别、高风险、成熟B细胞非霍奇金淋巴瘤患者的无事件生存期和总生存期，并与低丙种球蛋白血症的发生率较高以及潜在的更多感染事件相关。（由法国卫生部临床研究医院计划和其他机构资助; ClinicalTrials.gov编号，NCT 01516580。
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. 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. 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. 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. (Funded by the Clinical Research Hospital Program of the French Ministry of Health and others; ClinicalTrials.gov number, NCT01516580.)