Department of Leukemia.
Department of Genomic Medicine, and.
Blood Adv. 2019 May 14;3(9):1533-1539. doi: 10.1182/bloodadvances.2019031336.
This phase 2 study was conducted to prospectively evaluate how clinical and biological factors correlate with outcome in patients with treatment-naive (TN) and relapsed (R) chronic lymphocytic leukemia (CLL) treated with lenalidomide and rituximab. Oral lenalidomide 10 mg was administered daily starting on day 9 of cycle 1. IV rituximab 375 mg/m was administered weekly during cycle 1 and every 4 weeks for cycles 3 to 12. Sequencing of a custom panel of 295 genes was performed in pretreatment bone marrow samples. The study included 61 patients with TN CLL and 59 with R CLL; the overall response rate (ORR) was 73% and 64%, respectively. A baseline β-microglobulin level <4 mg/L was associated with higher ORR in both groups (both, = .03), and absence of mutations in the NOTCH signaling pathway showed a trend for association with higher ORR in R CLL ( = .10). Median PFS was 50 months in TN patients and 28 months in R patients. On multivariate analysis, age ≥65 years ( = .02) was associated with shorter PFS in TN patients, whereas according to univariate analysis, >2 previous therapies ( = .02) was the only factor associated with shorter PFS in R patients. A trend for association between mutations in the NOTCH pathway and shorter PFS was observed in TN CLL ( = .15). Further exploration of the NOTCH pathway may help optimize the efficacy of this combination in patients with CLL. This study protocol was approved by the University of Texas MD Anderson Cancer Center institutional review board and registered at clinicaltrials.gov (#NCT01446133).
这项 2 期研究旨在前瞻性评估初治（TN）和复发（R）慢性淋巴细胞白血病（CLL）患者接受来那度胺和利妥昔单抗治疗时，临床和生物学因素与结局的相关性。第 1 周期第 9 天开始每日口服来那度胺 10mg。第 1 周期每周给予 IV 利妥昔单抗 375mg/m2，第 3 周期至第 12 周期每 4 周给予一次。在预处理骨髓样本中进行了 295 个基因定制面板的测序。该研究纳入了 61 例 TN CLL 患者和 59 例 R CLL 患者；总缓解率（ORR）分别为 73%和 64%。两组中基线β-微球蛋白水平<4mg/L 与更高的 ORR 相关（均为 P=.03），NOTCH 信号通路无突变与 R CLL 更高的 ORR 呈趋势相关（P=.10）。TN 患者的中位无进展生存期（PFS）为 50 个月，R 患者为 28 个月。多变量分析显示，年龄≥65 岁（P=.02）与 TN 患者 PFS 较短相关，而根据单变量分析，>2 次既往治疗（P=.02）是 R 患者 PFS 较短的唯一相关因素。TN CLL 中 NOTCH 通路突变与较短 PFS 之间存在相关性趋势（P=.15）。进一步探索 NOTCH 通路可能有助于优化该联合方案在 CLL 患者中的疗效。该研究方案经德克萨斯大学 MD 安德森癌症中心机构审查委员会批准，并在 clinicaltrials.gov 上注册（#NCT01446133）。
