Department of Hematology and Lymphoma and Myeloma Center Amsterdam, Academic Medical Center, Amsterdam
Department of Hematology and Lymphoma and Myeloma Center Amsterdam, Academic Medical Center, Amsterdam.
Haematologica. 2019 Jan;104(1):147-154. doi: 10.3324/haematol.2018.193854. Epub 2018 Aug 16.
Lenalidomide has been proven to be effective but with a distinct and difficult to manage toxicity profile in the context of chronic lymphocytic leukemia, potentially hampering combination treatment with this drug. We conducted a phase 1-2 study to evaluate the efficacy and safety of six cycles of chlorambucil (7 mg/m daily), rituximab (375 mg/m cycle 1 and 500 mg/m cycles 2-6) and individually-dosed lenalidomide (escalated from 2.5 mg to 10 mg) (induction-I) in first-line treatment of patients with chronic lymphocytic leukemia unfit for treatment with fludarabine, cyclophosphamide and rituximab. This was followed by 6 months of 10 mg lenalidomide monotherapy (induction-II). Of 53 evaluable patients in phase 2 of the study, 47 (89%) completed induction-I and 36 (68%) completed induction-II. In an intention-to-treat analysis, the overall response rate was 83%. The median progression-free survival was 49 months, after a median follow-up time of 27 months. The 2- and 3-year progression-free survival rates were 58% and 54%, respectively. The corresponding rates for overall survival were 98% and 95%. No tumor lysis syndrome was observed, while tumor flair reaction occurred in five patients (9%, 1 grade 3). The most common hematologic toxicity was grade 3-4 neutropenia, which occurred in 73% of the patients. In conclusion, addition of lenalidomide to a chemotherapy backbone followed by a fixed duration of lenalidomide monotherapy resulted in high remission rates and progression-free survival rates, which seem comparable to those observed with novel drug combinations including novel CD20 monoclonal antibodies or kinase inhibitors. Although lenalidomide-specific toxicity remains a concern, an individualized dose-escalation schedule is feasible and results in an acceptable toxicity profile. .
来那度胺在慢性淋巴细胞白血病的治疗中已被证实有效，但具有明显且难以控制的毒性特征，可能会影响该药物与其他药物的联合治疗。我们进行了一项 1 期-2 期研究，评估 6 个周期的苯丁酸氮芥（每天 7mg/m2）、利妥昔单抗（第 1 周期 375mg/m2，第 2-6 周期 500mg/m2）和个体化剂量来那度胺（起始剂量 2.5mg，逐渐增至 10mg）（诱导-I）在不适合氟达拉滨、环磷酰胺和利妥昔单抗治疗的慢性淋巴细胞白血病患者一线治疗中的疗效和安全性。随后进行 6 个月的 10mg 来那度胺单药治疗（诱导-II）。在研究的 2 期 53 例可评估患者中，47 例（89%）完成诱导-I，36 例（68%）完成诱导-II。意向治疗分析中，总缓解率为 83%。中位无进展生存期为 49 个月，中位随访时间为 27 个月。2 年和 3 年无进展生存率分别为 58%和 54%，总生存率相应为 98%和 95%。未观察到肿瘤溶解综合征，而 5 例患者（9%，3 级 1 例）出现肿瘤 flares 反应。最常见的血液学毒性是 3-4 级中性粒细胞减少症，发生于 73%的患者。总之，在化疗方案基础上加用来那度胺，随后进行固定疗程的来那度胺单药治疗，可获得较高的缓解率和无进展生存率，这与新型药物联合治疗（包括新型 CD20 单克隆抗体或激酶抑制剂）观察到的结果相似。虽然来那度胺特异性毒性仍然是一个问题，但个体化剂量递增方案是可行的，可获得可接受的毒性特征。
