Brown Jennifer R, Hallek Michael J, Pagel John M
From the Dana-Farber Cancer Institute, Boston, MA; University Hospital of Cologne, Cologne, Germany; Swedish Cancer Institute, Seattle, WA.
Am Soc Clin Oncol Educ Book. 2016;35:e387-98. doi: 10.1200/EDBK_159018.
During the past 5 years, rapid therapeutic advances have changed the landscape of chronic lymphocytic leukemia (CLL) therapy. This disease has traditionally been treated using cytotoxic chemotherapy regimens in combination with anti-CD20 antibody treatment, and recent long-term follow-up data from multiple centers suggest that fit patients with CLL with favorable disease features-particularly mutated immunoglobulin heavy chain variable region (IGHV) genes-derive very long-term benefit from the most potent of these regimens, namely the fludarabine, cyclophosphamide, and rituximab (FCR) regimen. The advent of oral targeted therapies, particularly ibrutinib and idelalisib, has provided generally well-tolerated and highly effective additional options that have come into widespread use in the relapsed setting. Additional agents are advancing in clinical development, with the BCL-2 inhibitor venetoclax likely to be approved by the U.S. Food and Drug Administration (FDA) in 2016. With the development of these novel therapies for patients with relapsed CLL, many unanswered questions remain, including the optimal sequence (first vs. second line), duration, discontinuation, and combination of these agents. In addition, recent publications show the emergence of a pattern of treatment resistance in certain subgroups of patients with del(17p) and complex karyotype that needs further study and improvement. Because the field of CLL management has become much more complex, we focus here on understanding the recent data and discuss many of the questions and controversies important for how we approach patients with CLL.
在过去5年中，治疗方面的快速进展改变了慢性淋巴细胞白血病（CLL）的治疗格局。传统上，这种疾病采用细胞毒性化疗方案联合抗CD20抗体治疗，多个中心最近的长期随访数据表明，具有良好疾病特征的适合CLL患者——尤其是免疫球蛋白重链可变区（IGHV）基因突变的患者——能从这些最有效的方案中获得非常长期的益处，即氟达拉滨、环磷酰胺和利妥昔单抗（FCR）方案。口服靶向治疗药物的出现，尤其是伊布替尼和艾代拉里斯，提供了耐受性普遍良好且高效的额外选择，已在复发情况下广泛应用。其他药物正在进行临床开发，BCL-2抑制剂维奈托克可能于2016年获得美国食品药品监督管理局（FDA）批准。随着这些针对复发CLL患者的新型疗法的发展，许多问题仍未得到解答，包括这些药物的最佳使用顺序（一线还是二线）、疗程、停药以及联合使用等。此外，最近的出版物显示，在某些伴有del(17p)和复杂核型的患者亚组中出现了治疗耐药模式，需要进一步研究和改进。由于CLL管理领域变得更加复杂，我们在此重点关注理解近期数据，并讨论许多对于我们如何治疗CLL患者很重要的问题和争议。
