Sharma Kamal, Janik John E, O'Mahony Deirdre, Stewart Donn, Pittaluga Stefania, Stetler-Stevenson Maryalice, Jaffe Elaine S, Raffeld Mark, Fleisher Thomas A, Lee Cathryn C, Steinberg Seth M, Waldmann Thomas A, Morris John C
Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland.
Clin Cancer Res. 2017 Jan 1;23(1):35-42. doi: 10.1158/1078-0432.CCR-16-1022. Epub 2016 Aug 2.
Therapeutic regimens for adult T-cell leukemia/lymphoma (ATL) are limited with unsatisfactory results, thereby warranting development of novel therapies. This study investigated antitumor activity and toxicity of alemtuzumab with regard to response, duration of response, progression-free survival, and overall survival in patients with human T-cell lymphotropic virus-1 (HTLV-1)-associated ATL.
Twenty-nine patients with chronic, acute, and lymphomatous types of ATL were enrolled in a single-institution, nonrandomized, open-label phase II trial wherein patients received intravenous alemtuzumab 30 mg three times weekly for a maximum of 12 weeks.
Twenty-nine patients were evaluable for response and toxicity. The overall objective response was 15 of 29 patients [95% confidence interval (CI), 32.5%-70.6%]. The 15 patients who responded manifested a median time to response of 1.1 months. Median response duration was 1.4 months for the whole group and 14.5 months among responders. Median progression-free survival was 2.0 months. Median overall survival was 5.9 months. The most common adverse events were 2 with vasovagal episodes (7%) and 3 with hypotensive episodes (10%), leukopenia (41%) grade 3 and (17%) grade 4, lymphocytopenia (59%) grade 3, neutropenia (31%) grade 3, anemia (24%), and thrombocytopenia (10%). All patients developed cytomegalovirus antigenemia (CMV). Three were symptomatic and all responded to antiviral therapy. Grade 3 or 4 infections were reported in 4 (14%) of patients.
Alemtuzumab induced responses in patients with acute HTLV-1-associated ATL with acceptable toxicity, but with short duration of responses. These studies support inclusion of alemtuzumab in novel multidrug therapies for ATL. Clin Cancer Res; 23(1); 35-42. ©2016 AACR.
成人T细胞白血病/淋巴瘤（ATL）的治疗方案有限且效果不尽人意，因此需要开发新的治疗方法。本研究调查了阿仑单抗在人T细胞嗜淋巴细胞病毒1型（HTLV-1）相关ATL患者中的抗肿瘤活性及毒性，包括反应情况、反应持续时间、无进展生存期和总生存期。
29例慢性、急性和淋巴瘤型ATL患者参加了一项单机构、非随机、开放标签的II期试验，患者接受静脉注射阿仑单抗30mg，每周3次，最多12周。
29例患者可评估反应和毒性。29例患者中有15例获得总体客观反应[95%置信区间（CI），32.5%-70.6%]。15例有反应的患者中位反应时间为1.1个月。整个组的中位反应持续时间为1.4个月，有反应者为14.5个月。中位无进展生存期为2.0个月。中位总生存期为5.9个月。最常见的不良事件为2例血管迷走神经发作（7%）和3例低血压发作（10%），3级白细胞减少（41%）和4级（17%），3级淋巴细胞减少（59%），3级中性粒细胞减少（31%），贫血（24%）和血小板减少（10%）。所有患者均出现巨细胞病毒血症（CMV）。3例有症状，均对抗病毒治疗有反应。4例（14%）患者报告有3级或4级感染。
阿仑单抗可使急性HTLV-1相关ATL患者产生反应，毒性可接受，但反应持续时间短。这些研究支持将阿仑单抗纳入ATL的新型多药治疗方案中。临床癌症研究；23(1)；35-42。©2016美国癌症研究协会。
