Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine.
Alemtuzumab in previously treated chronic lymphocytic leukemia patients who also had received fludarabine.
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DOI：
10.1200/jco.2002.06.119
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发表时间：
2002-09
期刊：
影响因子：
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通讯作者：
K. Rai;C. Freter;R. Mercier;M. Cooper;B. Mitchell;E. Stadtmauer;P. Santabarbara;B. Wacker;L. Brettman
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文献类型：
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作者：
K. Rai;C. Freter;R. Mercier;M. Cooper;B. Mitchell;E. Stadtmauer;P. Santabarbara;B. Wacker;L. Brettman
目的这项第二阶段的初步研究确定了阿伦图珠单抗(CamPath-1H；英国Burroughs Wellcome)治疗慢性淋巴细胞白血病(CLL)的有效性和安全性，这些患者都曾接受过氟达拉滨和其他化疗方案。患者和方法24名患者在美国的6个中心接受阿伦图珠单抗静脉注射治疗。目标剂量为30毫克，每周三次，持续2小时，最长持续16周。回答由一个独立的专家小组使用1996年国家癌症研究所赞助的工作组标准进行评估。安全性评估包括淋巴细胞亚群分析。抗菌预防并不是强制性的。结果8例(33%)患者完全缓解，中位缓解时间为3.9个月(1.6~5.3个月)。中位有效时间为15.4个月(4.6~38.0个月)，中位疾病进展时间19.6个月(7.7~42.0个月)，中位生存期35.8个月(8.8~47.1个月)。急性输液相关事件，主要是1级和2级，在第一周是最常见和最严重的。10名患者(8名无反应者和2名应答者)在研究中经历了重大感染。研究中有两名患者报告了卡氏肺孢子虫肺炎，两名患者均未接受预防。中位数的CD4+和CD8+计数在研究结束时下降，然后开始上升，并在1个月的随访中进一步恢复。从10名患者获得的53份样本中，有一份的阿伦图祖玛抗体效价较低。结论Alemtuzumab对接受氟达拉滨治疗的预后不良的CLL患者有显著的疗效。然而，由于机会性感染的发生率相对较高，并伴有严重的淋巴细胞减少症，未来的方案应该包括强制性预防。
PURPOSE This phase II pilot study determined the efficacy and safety of alemtuzumab (Campath-1H; Burroughs Wellcome, United Kingdom) in patients with chronic lymphocytic leukemia (CLL), all of whom had previously received fludarabine and other chemotherapy regimens. PATIENTS AND METHODS Twenty-four patients were treated with intravenous alemtuzumab at six centers in the United States. The target dose of 30 mg over 2 hours, three times weekly, was administered for up to 16 weeks. Responses were evaluated by an independent panel of experts using 1996 National Cancer Institute-sponsored Working Group criteria. Safety assessments included analysis of lymphocyte subpopulations. Antimicrobial prophylaxis was not mandatory. RESULTS Eight patients (33%) achieved a major response (all partial remissions), with a median time to response of 3.9 months (range, 1.6 to 5.3 months). The median duration of response was 15.4 months (range, 4.6 to >or= 38.0 months), the median time to disease progression was 19.6 months (range, 7.7 to >or= 42.0 months), and the median survival time was 35.8 months (range, 8.8 to >or= 47.1 months). Acute infusion-related events, mainly grades 1 and 2, were most common and most severe in the first week. Ten patients (eight nonresponders and two responders) experienced major infections on-study. Pneumocystis carinii pneumonia was reported in two patients on-study; neither had received prophylaxis. Median CD4+ and CD8+ counts decreased and then began to increase by the end of the study, with further recovery by 1-month follow-up. One of 53 samples obtained from 10 patients had a low titer of alemtuzumab antibodies. CONCLUSION Alemtuzumab has significant activity in poor-prognosis, fludarabine-treated CLL patients. However, because of a relatively high incidence of opportunistic infections accompanying profound lymphopenia, future protocols should include mandatory prophylaxis.