Phase II Window Study on Rituximab in Newly Diagnosed Pediatric Mature B-Cell Non-Hodgkin's Lymphoma and Burkitt Leukemia
Phase II Window Study on Rituximab in Newly Diagnosed Pediatric Mature B-Cell Non-Hodgkin's Lymphoma and Burkitt Leukemia
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DOI：
10.1200/jco.2009.26.6791
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发表时间：
2010-07-01
影响因子：
45.3
通讯作者：
Reiter, Alfred
中科院分区：
文献类型：
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作者：
Meinhardt, Andrea;Burkhardt, Birgit;Reiter, Alfred
目的利妥昔单抗在儿童B细胞非霍奇金淋巴瘤（B-NHL）中的活性尚未确定。我们进行了一项II期窗口研究，以检查利妥昔单抗在新诊断的儿科B-NHL中的活性和耐受性。患者和方法19岁以下患有CD 20（+）B-NHL且至少有一个可测量部位的患者符合资格。治疗包括第1天静脉注射利妥昔单抗375 mg/m2;合并治疗包括第1天和第3天鞘内注射拉布立酶（IT）三联药物（甲氨蝶呤、阿糖胞苷和泼尼松龙）治疗CNS阳性患者，仅类固醇治疗过敏反应。反应标准是在利妥昔单抗前24小时内和第5天1至3个病灶的两个最大垂直直径和/或骨髓（BM）或外周血（PB）中原始细胞百分比的乘积。应答者至少有一个病灶或BM或PB原始细胞减少>= 25%，其他部位无疾病进展。反应率（RR）设定为45%不利的活动或在65%有利activity.ResultsFrom 2004年4月至2008年8月，136例患者入组。国家癌症研究所常见毒性标准3/4可归因于利妥昔单抗的毒性为一般状况，15%;疲劳，13%;过敏反应，7%;感染，3%;谷草转氨酶/谷氨酰胺转氨酶，8%;无毛细血管渗漏;无中毒性死亡。49例患者因退出研究（n = 16）、CNS阴性患者接受IT治疗（n = 8）、皮质类固醇治疗（n = 3）、缓解评价技术不充分（n = 21）或无可评价病变（n = 1）而无法评价缓解。在87例可评价患者中，36例为应答者（RR，41.4%; 95%CI，31%-52%）;其中，67例伯基特淋巴瘤中有27例，15例弥漫性大B细胞淋巴瘤中有7例。与实体瘤病灶（36/108; P = 0.007）相比，BM（12/18）的反应更频繁。结论利妥昔单抗作为单药治疗儿童B-NHL是有效的，即使RR低于II期计划中要求的。
PurposeThe activity of rituximab in pediatric B-cell non-Hodgkin's lymphoma (B-NHL) has not yet been determined. We conducted a phase II window study to examine activity and tolerability of rituximab in newly diagnosed pediatric B-NHL.Patients and MethodsPatients younger than age 19 years with CD20(+) B-NHL with at least one measurable site were eligible. Treatment consisted of rituximab at 375 mg/m(2) administered intravenously on day 1; concomitant therapy consisted of rasburicase, intrathecally (IT) triple drug (methotrexate, cytarabine, and prednisolone) on days 1 and 3 for CNS-positive patients and steroids only for anaphylaxis. Response criterion was the product of the two largest perpendicular diameters of one to three lesions and/or the percentage of blasts in bone marrow (BM) or peripheral blood (PB) within 24 hours before rituximab and on day 5. Responders had >= 25% decrease of at least one lesion or BM or PB blasts and no disease progress at other sites. Response rate (RR) was set at 45% for unfavorable activity or at 65% for favorable activity.ResultsFrom April 2004 to August 2008, 136 patients were enrolled. National Cancer Institute Common Toxicity Criteria 3/4 toxicities attributable to rituximab were general condition, 15%; fatigue, 13%; anaphylaxis, 7%; infection, 3%; glutamic-oxaloacetic transaminase/glutamic-pyruvic transaminase, 8%; no capillary leakage; and no toxic death. Forty-nine patients were not evaluable for response because of withdrawal from the study (n = 16), IT therapy in CNS-negative patients (n = 8), corticosteroid treatment (n = 3), technical inadequacy of response evaluation (n = 21), or no evaluable lesion (n = 1). Of 87 evaluable patients, 36 were responders (RR, 41.4%; 95% CI, 31% to 52%); among them, 27 of 67 with Burkitt lymphoma and seven of 15 with diffuse large B-cell lymphoma. A response was more frequently observed in BM (12 of 18) compared with solid tumor lesions (36 of 108; P = .007).Conclusion Rituximab is active as a single-agent in pediatric B-NHL even though the RR was lower than requested in the phase II plan.