O'Brien Susan M, Kantarjian Hagop M, Thomas Deborah A, Cortes Jorge, Giles Francis J, Wierda William G, Koller Charles A, Ferrajoli Alessandra, Browning Mary, Lerner Susan, Albitar Maher, Keating Michael J
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer. 2003 Dec 15;98(12):2657-63. doi: 10.1002/cncr.11871.
The objective of this study was to investigate the efficacy and safety of alemtuzumab, the humanized anti-CD52 monoclonal antibody, in patients with B-cell chronic lymphocytic leukemia and residual disease after chemotherapy.
Forty-one patients received alemtuzumab 3 times weekly for 4 weeks. The first 24 patients received 10 mg per dose, and the next 17 patients received 30 mg. All patients received infection prophylaxis during therapy and for 2 months after treatment.
The overall response rate was 46%, including 39% of patients who received the 10 mg dose and responded versus 56% of the patients who received the 30 mg dose. The major reason for failure to respond was the presence of adenopathy. Residual bone marrow disease cleared in most patients, and 11 of 29 patients (38%) achieved a molecular disease remission. The median time to disease progression had not been reached in responders with a median follow-up of 18 months. Six patients remained in disease remission between 24-38 months after therapy. Infusion-related events were common with the initial doses, but all such events were NCI Common Toxicity Criteria Grade 1-2. Infections were reported to occur in 15 patients (37%), and 9 of these infections were reactivation of cytomegalovirus. Three patients developed Epstein-Barr virus positive, large cell lymphoma. Two patients had spontaneous resolution of the lymphoma and, in one patient, the lymphoma resolved after treatment with cidofovir and immunoglobulin.
Alemtuzumab produced significant responses in patients with residual disease after chemotherapy. Bone marrow disease was eradicated more frequently than lymph node disease, and molecular disease remissions were achieved. A randomized trial comparing alemtuzumab with observation after chemotherapy is indicated.
本研究旨在探讨人源化抗CD52单克隆抗体阿仑单抗对化疗后残留疾病的B细胞慢性淋巴细胞白血病患者的疗效和安全性。
41例患者每周接受3次阿仑单抗治疗，共4周。前24例患者每剂接受10mg，后17例患者每剂接受30mg。所有患者在治疗期间及治疗后2个月接受感染预防。
总缓解率为46%，其中接受10mg剂量且有反应的患者为39%，接受30mg剂量的患者为56%。无反应的主要原因是存在腺病。大多数患者残留的骨髓疾病清除，29例患者中有11例（38%）实现分子疾病缓解。反应者的疾病进展中位时间未达到，中位随访时间为18个月。6例患者在治疗后24 - 38个月保持疾病缓解。输注相关事件在初始剂量时常见，但所有此类事件均为美国国立癌症研究所常见毒性标准1 - 2级。据报告15例患者（37%）发生感染，其中9例感染为巨细胞病毒再激活。3例患者发生EB病毒阳性大细胞淋巴瘤。2例患者淋巴瘤自发缓解，1例患者经西多福韦和免疫球蛋白治疗后淋巴瘤缓解。
阿仑单抗对化疗后残留疾病的患者产生了显著反应。骨髓疾病比淋巴结疾病更频繁地根除，且实现了分子疾病缓解。表明需要进行一项比较阿仑单抗与化疗后观察的随机试验。
