Phase II Study of Alemtuzumab (CAMPATH-1) in Patients with HTLV-1-Associated Adult T-cell Leukemia/lymphoma.
Phase II Study of Alemtuzumab (CAMPATH-1) in Patients with HTLV-1-Associated Adult T-cell Leukemia/lymphoma.
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DOI：
10.1158/1078-0432.ccr-16-1022
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发表时间：
2017-01-01
期刊：
影响因子：
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通讯作者：
Morris JC
中科院分区：
文献类型：
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作者：
Sharma K;Janik JE;O'Mahony D;Stewart D;Pittaluga S;Stetler-Stevenson M;Jaffe ES;Raffeld M;Fleisher TA;Lee CC;Steinberg SM;Waldmann TA;Morris JC
ATL的治疗方案是有限的，结果不令人满意，因此需要开发新的治疗方法。这项研究调查了阿仑单抗在人类t细胞嗜淋巴病毒-1 （HTLV-1）相关成人t细胞白血病/淋巴瘤（ATL）患者的反应、反应持续时间、无进展生存期和总生存期方面的抗肿瘤活性和毒性。29名慢性、急性和淋巴瘤型ATL患者入组了一项单机构、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，最长12周。29例患者可评估反应和毒性。总体客观缓解为29例患者中的15例（95% CI: 32.5 - 70.6%）。有应答的15例患者的中位应答时间为1.1个月。整个组的中位反应持续时间为1.4个月，应答者为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。最常见的不良事件是2例血管迷走神经性发作（7%）和3例低血压发作（10%），白细胞减少（41%）3级和（17%）4级，淋巴细胞减少（59%）3级，中性粒细胞减少（31%）3级，贫血（24%）和血小板减少10%。所有患者均出现巨细胞病毒抗原血症（CMV）。其中3例出现症状，抗病毒治疗均有效。4例（14%）患者报告了3级或4级感染。阿仑单抗在急性htlv -1相关ATL患者中诱导反应，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。
Therapeutic regimens for 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 adult T-cell leukemia/lymphoma (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 out of 29 patients (95% CI: 32.5 to 70.6%). The 15 patients that 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 multi-drug therapies for ATL.