Danelle F. James, Januario E. Castro, Andrew Greaves, Laura Z. Rassenti, Thomas J. Kipps, Moores Cancer Center, University of California San Diego, La Jolla, CA; Lillian Werner, Jennifer R. Brown, Donna Neuberg, Dana-Farber Cancer Institute, Boston, MA; William G. Wierda, MD Anderson Cancer Center, The University of Texas, Houston, TX; Jacqueline C. Barrientos, Kanti R. Rai, North Shore-Long Island Jewish Health System, New Hyde Park, NY; Amy J. Johnson, The Ohio State University, Columbus, OH.
J Clin Oncol. 2014 Jul 1;32(19):2067-73. doi: 10.1200/JCO.2013.51.5890. Epub 2014 May 27.
Lenalidomide is an immunomodulatory agent with therapeutic activity in chronic lymphocytic leukemia (CLL). In preclinical models, lenalidomide acted synergistically with rituximab. The CLL Research Consortium initiated a phase II study to evaluate this combination in treatment-naive patients.
Lenalidomide was initiated at 2.5 mg/day and was escalated based on treatment tolerability to a maximum of 10 mg/day, for 21 days/cycle, for a maximum of seven cycles. Rituximab was administered at the end of cycle 1 and was continued for seven cycles. Patients received allopurinol and aspirin for prophylaxis.
Sixty-nine patients enrolled onto one of two age-specific strata; patients' median age was 56 and 70 years for arms A and B, respectively. Patients in the older-patient stratum more frequently had elevated serum beta-2 microglobulin levels, high-risk Rai stage, and were less likely to complete the maximum planned therapy. Adverse events were similar in the two arms. Nonhematologic toxicity was predominantly at grade 1/2, and neutropenia was the most common hematologic adverse event. The response rate for arm A was 95%, with 20% complete responses (CRs) and 20% nodular partial responses. Of arm B patients, 78% achieved a response, of which 11% were CRs. Median progression-free survival (PFS) was 19 months for the younger cohort and 20 months for the older cohort.
Intrapatient dose-escalation was safe. The majority of patients reached the maximum lenalidomide dose and experienced a response to a defined seven-cycle course of lenalidomide and rituximab therapy. Despite differences in baseline characteristics and the response rate between the two strata, the PFS did not differ.
来那度胺是一种免疫调节药物，在慢性淋巴细胞白血病（CLL）中有治疗活性。在临床前模型中，来那度胺与利妥昔单抗协同作用。CLL 研究联盟启动了一项 II 期研究，以评估该联合方案在初治患者中的疗效。
来那度胺起始剂量为 2.5mg/天，并根据治疗耐受性逐渐增加剂量，最高可达 10mg/天，每 21 天为一个周期，最多 7 个周期。利妥昔单抗在第 1 个周期结束时给药，并继续使用 7 个周期。患者接受别嘌醇和阿司匹林预防。
69 名患者分别入组了两个年龄亚组之一；患者的中位年龄分别为 56 岁和 70 岁。老年患者亚组中β2 微球蛋白水平升高、高危 Rai 分期和完成最大计划治疗的可能性较低的患者更为常见。两个治疗组的不良反应相似。非血液学毒性主要为 1/2 级，中性粒细胞减少症是最常见的血液学不良事件。A 组的缓解率为 95%，其中 20%完全缓解（CR）和 20%结节部分缓解。B 组患者的缓解率为 78%，其中 11%为 CR。年轻队列的中位无进展生存期（PFS）为 19 个月，老年队列为 20 个月。
个体内剂量递增是安全的。大多数患者达到了来那度胺的最大剂量，并对确定的 7 个周期的来那度胺和利妥昔单抗治疗有反应。尽管两个亚组之间的基线特征和缓解率存在差异，但 PFS 没有差异。
