Ferrajoli Alessandra, O'Brien Susan M, Cortes Jorge E, Giles Francis J, Thomas Deborah A, Faderl Stefan, Kurzrock Razelle, Lerner Susan, Kontoyiannis Dimitrios P, Keating Michael J
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2003 Aug 15;98(4):773-8. doi: 10.1002/cncr.11551.
Pilot studies showed that alemtuzumab is active in lymphoproliferative disorders. The authors conducted a Phase II trial to evaluate the efficacy and safety of alemtuzumab in advanced or refractory chronic lymphoproliferative disorders.
Seventy-eight patients were enrolled. The most common diagnoses were chronic lymphocytic leukemia (n = 42 patients) and T-cell prolymphocytic leukemia (n = 18 patients). Before entering the study, the patients had received multiple therapies (median, three therapies) and the median time from diagnosis was 7 years. Alemtuzumab was given intravenously at doses of 3 mg, 10 mg, and 30 mg on 3 consecutive days, after which 30 mg was administered 3 times a week. Patients were treated for 4-12 weeks depending on disease response. All patients received prophylactic trimethoprim/sulfamethoxazole and valacyclovir.
The overall response rate was 35%, the complete response (CR) rate was 13%, and the partial response (PR) rate was 22%. The median duration of response was 18 months for patients achieving a CR and 7 months for patients achieving a PR. The median duration of survival was 25 months for patients who had a response and 12 months for the entire population. Normalization of the lymphocyte count was observed in 84% of patients and resolution of bone marrow involvement was observed in 49% of patients. The most common infusion-related adverse events were fever, rigors, skin rash, nausea, and dyspnea. These were most common during the first week of therapy. Hematologic toxicity was comprised of long-lasting lymphocytopenia and transient neutropenia and thrombocytopenia. Thirty-six patients (46%) experienced at least one episode of fever or infection.
Alemtuzumab has a high response rate in patients with chronic lymphoproliferative disorders.
前期研究表明阿仑单抗对淋巴增殖性疾病有效。作者开展了一项II期试验，以评估阿仑单抗治疗晚期或难治性慢性淋巴增殖性疾病的疗效和安全性。
纳入78例患者。最常见的诊断为慢性淋巴细胞白血病（42例患者）和T细胞幼淋巴细胞白血病（18例患者）。入组研究前，患者接受过多种治疗（中位数为3种治疗），从诊断到入组的中位时间为7年。阿仑单抗连续3天静脉给药，剂量分别为3mg、10mg和30mg，之后每周给药3次，每次30mg。根据疾病反应情况，患者接受4 - 12周的治疗。所有患者均接受预防性甲氧苄啶/磺胺甲恶唑和伐昔洛韦治疗。
总缓解率为35%，完全缓解（CR）率为13%，部分缓解（PR）率为22%。达到CR的患者缓解持续时间中位数为18个月，达到PR的患者为7个月。有反应的患者生存时间中位数为25个月，全体患者为12个月。84%的患者淋巴细胞计数恢复正常，49%的患者骨髓受累情况得到缓解。最常见的输液相关不良事件为发热、寒战、皮疹、恶心和呼吸困难。这些不良事件在治疗的第一周最为常见。血液学毒性包括持续性淋巴细胞减少以及短暂性中性粒细胞减少和血小板减少。36例患者（46%）至少经历过一次发热或感染。
阿仑单抗治疗慢性淋巴增殖性疾病患者的缓解率较高。
