Elter Thomas, Hallek Michael, Montillo Marco
Department of Internal Medicine, Center for Integrated Oncology Cologne-Bonn, University of Cologne, Cologne, Germany.
Clin Adv Hematol Oncol. 2011 May;9(5):364-73.
Over the past decade, the use of the monoclonal antibody alemtuzumab in chronic lymphocytic leukemia has expanded from administration as a single-agent therapy, into use in combination with fludarabine or rituximab, and further to use as a consolidation agent with the goal of eradicating minimal residual disease. Numerous clinical studies have shown that alemtuzumab is effective as first-line treatment and in patients who have relapsed disease or who are refractory to fludarabine. Despite improvements in response rates and survival compared with combination chemotherapy, there remains some hesitation to incorporate alemtuzumab into management because of known toxicities. Adverse events in patients treated with standard-dose, single-agent alemtuzumab occur at generally predictable time points during treatment and can be managed effectively; this outcome is less established when alemtuzumab is incorporated into combination regimens. Variability in alemtuzumab dosing, route of administration, and duration of therapy has led to inconsistent and sometimes adverse safety consequences. This article presents an overview of clinical studies with alemtuzumab as a single agent, in combination, or in consolidation, with discussion of toxicity and suggestions for ensuring that the efficacious outcomes following alemtuzumab therapy are not outweighed by safety concerns.
在过去十年中，单克隆抗体阿仑单抗在慢性淋巴细胞白血病治疗中的应用，已从作为单一药物治疗扩展到与氟达拉滨或利妥昔单抗联合使用，进而用作巩固治疗药物，目标是根除微小残留病。大量临床研究表明，阿仑单抗作为一线治疗药物，对复发或对氟达拉滨耐药的患者有效。尽管与联合化疗相比，缓解率和生存率有所提高，但由于已知的毒性，在将阿仑单抗纳入治疗方案时仍存在一些犹豫。接受标准剂量单药阿仑单抗治疗的患者不良事件通常在治疗期间可预测的时间点发生，并且可以有效处理；当阿仑单抗纳入联合治疗方案时，这种结果尚不太明确。阿仑单抗给药剂量、给药途径和治疗持续时间的差异导致了不一致的、有时甚至是不良的安全后果。本文概述了阿仑单抗作为单一药物、联合用药或巩固治疗的临床研究，讨论了毒性问题，并提出了确保阿仑单抗治疗后的有效结果不会被安全问题所抵消的建议。
