Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Ther Clin Risk Manag. 2010 Dec 22;7:1-11. doi: 10.2147/TCRM.S5855.
Chronic lymphocytic leukemia (CLL) is a biologically heterogeneous illness that primarily afflicts the elderly. For many decades, the initial therapy for most patients requiring treatment was limited to single-agent alkylator therapy. Within the last two decades, we have seen remarkable progress in understanding the biology of CLL and the development of more effective treatment strategies that have employed monoclonal antibodies, such as rituximab (anti-CD20). Furthermore, recognition of the synergy between fludarabine, cyclophosphamide, and rituximab (FCR) prompted investigators to explore the clinical activity of FCR in Phase II and III trials in patients with relapsed/refractory or previously untreated CLL. On the basis of these findings, the US Food and Drug Administration (FDA) recently approved rituximab in combination with fludarabine and cyclophosphamide for the treatment of patients with relapsed/refractory or previously untreated CD20-postive CLL. Recent data from a randomized Phase III trial has confirmed improved overall survival with FCR in patients with previously untreated CLL. However, FCR is not for everyone. More tolerable regimens using rituximab for the elderly and less fit patients are being pursued in clinical trials. Recent Phase II trials have explored potentially less myelosuppressive approaches by using lower doses of fludarabine and cyclophosphamide, replacing fludarabine with pentostatin, and combining rituximab with chlorambucil. Furthermore new biomarkers predictive of early disease progression have prompted investigators to explore the benefits of early treatment with rituximab combined with other agents. In addition to the proven utility of rituximab as a frontline agent for CLL, rituximab has a favorable toxicity profile both as a single agent and in combination with chemotherapy. The majority of adverse events are Grade 1 and 2 infusion-related reactions (fevers, chills, and rigors) and occur with the first dose of rituximab. The improved tolerability observed with second and subsequent infusions allows for shorter infusion times. Rituximab's proven activity and favorable toxicity profile has made it an ideal agent for expanding treatment options for patients with CLL, the majority of whom are elderly.
慢性淋巴细胞白血病（CLL）是一种生物学异质性疾病，主要影响老年人。几十年来，大多数需要治疗的患者的初始治疗方法仅限于单一药物烷化剂治疗。在过去的二十年中，我们在理解 CLL 的生物学和开发更有效的治疗策略方面取得了显著进展，这些策略采用了单克隆抗体，如利妥昔单抗（抗 CD20）。此外，人们认识到氟达拉滨、环磷酰胺和利妥昔单抗（FCR）之间的协同作用，促使研究人员在复发/难治性或未经治疗的 CLL 患者的 II 期和 III 期试验中探索 FCR 的临床活性。基于这些发现，美国食品和药物管理局（FDA）最近批准利妥昔单抗联合氟达拉滨和环磷酰胺用于治疗复发/难治性或未经治疗的 CD20 阳性 CLL 患者。最近一项随机 III 期试验的数据证实，FCR 可改善未经治疗的 CLL 患者的总生存期。然而，FCR 并不适合所有人。正在临床试验中探索更适合老年人和身体状况较差患者的耐受性更好的方案。最近的 II 期试验探索了通过使用较低剂量的氟达拉滨和环磷酰胺、用喷司他丁替代氟达拉滨以及联合利妥昔单抗和苯丁酸氮芥等潜在的低骨髓抑制方法。此外，新的生物标志物预测疾病早期进展，促使研究人员探索早期使用利妥昔单抗联合其他药物治疗的益处。除了利妥昔单抗作为 CLL 一线药物的已证实功效外，利妥昔单抗作为单一药物和联合化疗均具有良好的毒性特征。大多数不良事件是 1 级和 2 级输注相关反应（发热、寒战和肌痛），发生在利妥昔单抗的第一剂。第二次和随后的输注观察到的耐受性提高允许缩短输注时间。利妥昔单抗的已知活性和良好的毒性特征使其成为扩展 CLL 患者治疗选择的理想药物，其中大多数是老年人。
