Center for Blood Disorders and Stem Cell Transplantation, Swedish Cancer Institute, Seattle, Washington.
US Oncology Hematology Research Program, Rocky Mountain Cancer Centers, Aurora, Colorado.
Clin Adv Hematol Oncol. 2020 Dec;18 Suppl 20(12):1-24.
In patients with follicular lymphoma, the prolonged clinical course consisting of multiple relapses is a fundamental challenge that requires clinicians to consider how to best balance treatment efficacy while minimizing toxicity and preserving quality of life. The treatment approaches and decisions regarding therapy are largely driven by the unique clinical features evident in each patient. The traditional treatment approaches for relapsed follicular lymphoma include chemoimmunotherapy regimens, targeted agents, radioimmunotherapy, and, occasionally, immunotherapy alone. The primary targeted agents used in the relapsed or refractory follicular lymphoma setting are the phosphatidylinositol 3-kinase (PI3K) inhibitors idelalisib, copanlisib, and duvelisib. PI3K inhibitors can have a significant toxicity profile. Radioimmunotherapy remains an underutilized option. The newest agent that has gained regulatory approval in the treatment of follicular lymphoma is tazemetostat, a methyltransferase inhibitor that inhibits and reduces the activity of EZH2. In June 2020, tazemetostat was approved by the US Food and Drug Administration (FDA) for the treatment of adult patients with relapsed or refractory follicular lymphoma who have tumors that are positive for an mutation (as detected by an FDA-approved test) and who have received at least 2 prior systemic therapies, or patients who have no satisfactory alternative treatment options. Data from a phase 2 study demonstrated that tazemetostat can produce clinically meaningful and durable responses, with a favorable safety profile, in heavily pretreated patients with or without an mutation.
在滤泡性淋巴瘤患者中，多次复发的长期临床病程是一个根本性的挑战，这需要临床医生考虑如何在最大限度地减少毒性和保持生活质量的同时，最好地平衡治疗效果。治疗方法和治疗决策在很大程度上取决于每个患者的独特临床特征。复发滤泡性淋巴瘤的传统治疗方法包括化疗免疫治疗方案、靶向药物、放射免疫治疗，偶尔也单独使用免疫治疗。在复发或难治性滤泡性淋巴瘤中使用的主要靶向药物是磷脂酰肌醇 3-激酶（PI3K）抑制剂idelalisib、copanlisib 和 duvelisib。PI3K 抑制剂可能具有显著的毒性特征。放射免疫治疗仍然是一种未充分利用的选择。在滤泡性淋巴瘤治疗中获得监管批准的最新药物是 tazemetostat，一种甲基转移酶抑制剂，可抑制和降低 EZH2 的活性。2020 年 6 月，tazemetostat 获得美国食品和药物管理局（FDA）批准，用于治疗复发或难治性滤泡性淋巴瘤的成年患者，这些患者的肿瘤存在 突变阳性（由 FDA 批准的检测方法检测到），并且已经接受了至少 2 种先前的系统治疗，或者患者没有满意的替代治疗选择。一项 2 期研究的数据表明，tazemetostat 可在有或没有 突变的预处理过的患者中产生具有临床意义和持久反应，且安全性良好。
