Kennedy G A, Seymour J F, Wolf M, Januszewicz H, Davison J, McCormack C, Ryan G, Prince H M
Haematology Service, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Eur J Haematol. 2003 Oct;71(4):250-6. doi: 10.1034/j.1600-0609.2003.00143.x.
Alemtuzumab (anti-CD52, Campath-1H) has recently been shown to be effective in the treatment of a range of hematological malignancies, including B-cell chronic lymphocytic leukemia and T-cell prolymphocytic leukemia. We undertook a phase II study to evaluate the safety, tolerability and efficacy of alemtuzumab in patients with relapsed or refractory advanced stage cutaneous T-cell lymphoma.
A total of eight patients were enrolled, seven with mycosis fungoides/Sézary syndrome (MF/SS) and one with large-cell transformation of MF. Seven patients had disease refractory to multiple previous therapies. Alemzumab (30 mg) was administered intravenously three times per week for 12 wk or until maximum response.
The overall response rate was 38%, with three patients achieving partial remission, two patients with stable disease and three patients with progressive disease (PD) during treatment. The time to progression was short, with all patients developing PD within 4 months of starting alemtuzumab. Response duration in the three PR patients was also brief, with responses lasting less than 3 months in all three cases. Significant hematological and immunosuppressive toxicity was observed, with both grade 3-4 cytopenias and significant infectious complications occurring in a majority of cases.
Our findings suggest that in heavily pretreated, refractory, advanced stage MF/SS, although alemtuzumab has biological activity, it is associated with significant toxicity and only modest clinical utility. As such, combination regimens incorporating alemtuzumab merit further investigation in this difficult to treat patient group.
阿仑单抗（抗CD52，Campath-1H）最近已被证明在治疗一系列血液系统恶性肿瘤中有效，包括B细胞慢性淋巴细胞白血病和T细胞幼淋巴细胞白血病。我们进行了一项II期研究，以评估阿仑单抗在复发或难治性晚期皮肤T细胞淋巴瘤患者中的安全性、耐受性和疗效。
共纳入8例患者，7例为蕈样肉芽肿/赛塞里综合征（MF/SS），1例为MF大细胞转化。7例患者对先前的多种治疗均难治。阿仑单抗（30mg）每周静脉注射3次，共12周或直至达到最大反应。
总缓解率为38%，3例患者达到部分缓解，2例患者病情稳定，3例患者在治疗期间病情进展（PD）。疾病进展时间较短，所有患者在开始使用阿仑单抗后4个月内均出现PD。3例PR患者的缓解持续时间也较短，3例患者的缓解均持续不到3个月。观察到显著的血液学和免疫抑制毒性，大多数病例出现3-4级血细胞减少和严重感染并发症。
我们的研究结果表明，在经过大量预处理、难治的晚期MF/SS患者中，尽管阿仑单抗具有生物学活性，但它与显著的毒性相关，临床效用有限。因此，在这个难以治疗的患者群体中，包含阿仑单抗的联合方案值得进一步研究。
