Lin Thomas S, Moran Mollie, Lucas Margaret, Waymer Sharon, Jefferson Sara, Fischer Diane B, Grever Michael R, Byrd John C
Division of Hematology and Oncology, Starling Loving Hall, Room 302, The Arthur James Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210, USA.
Hematol Oncol Clin North Am. 2004 Aug;18(4):895-913, ix-x. doi: 10.1016/j.hoc.2004.04.008.
Therapeutic options for chronic lymphocytic leukemia (CLL) have been limited, with low complete response rates (CR) and no treatments demonstrating a survival advantage. The recent introduction of the monoclonal antibodies rituximab and alemtuzumab into clinical trials for patients with CLL has generated promising results. Rituximab targets the CD20 antigen and demonstrates varied single-agent activity that is highly dependent upon the dosing schedule and treatment status of the patient. More importantly, when rituximab is combined with fludarabine or fludarabine and cyclophosphamide, a high frequency of CR and prolonged progression-free survival are observed without an appreciable increase in significant toxicity. Alemtuzumab targets the more ubiquitously expressed CD52 antigen and is therefore associated with a higher frequency of toxicity, particularly immunosuppression, but has appreciable activity in fludarabine refractory CLL. Additionally, alemtuzumab is effective against CLL clones that have p53 mutations or deletions. Future efforts in developing combination strategies with rituximab, alemtuzumab, and potentially other new antibodies offer great promise for the future treatment of CLL.
慢性淋巴细胞白血病（CLL）的治疗选择一直有限，完全缓解率（CR）较低，且尚无治疗方法显示出有生存优势。最近，单克隆抗体利妥昔单抗和阿仑单抗被引入CLL患者的临床试验，并产生了令人鼓舞的结果。利妥昔单抗靶向CD20抗原，其单药活性各异，高度依赖于给药方案和患者的治疗状态。更重要的是，当利妥昔单抗与氟达拉滨或氟达拉滨和环磷酰胺联合使用时，可观察到高频率的CR和延长的无进展生存期，且未出现明显的显著毒性增加。阿仑单抗靶向更广泛表达的CD52抗原，因此与更高频率的毒性相关，尤其是免疫抑制，但在氟达拉滨难治性CLL中具有可观的活性。此外，阿仑单抗对具有p53突变或缺失的CLL克隆有效。未来在开发利妥昔单抗、阿仑单抗以及可能的其他新抗体联合策略方面的努力为CLL的未来治疗带来了巨大希望。
