We report a randomized prospective phase 3 study (CLL7), designed to evaluate the efficacy of fludarabine, cyclophosphamide, and rituximab (FCR) in patients with an early-stage high-risk chronic lymphocytic leukemia (CLL). Eight hundred patients with untreated-stage Binet A disease were enrolled as intent-to-treat population and assessed for four prognostic markers: lymphocyte doubling time <12 months, serum thymidine kinase >10 U/L, unmutated IGHV genes, and unfavorable cytogenetics (del(11q)/del(17p)/trisomy 12). Two hundred and one patients with ≥2 risk features were classified as high-risk CLL and 1:1 randomized to receive either immediate therapy with 6xFCR (Hi-FCR, 100 patients), or to be observed according to standard of care (Hi-W&W, 101 patients). The overall response rate after early FCR was 92.7%. Common adverse events were hematological toxicities and infections (61.0%/41.5% of patients, respectively). After median observation time of 55.6 (0-99.2) months, event-free survival was significantly prolonged in Hi-FCR compared with Hi-W&W patients (median not reached vs. 18.5 months, p < 0.001). There was no significant overall survival benefit for high-risk patients receiving early FCR therapy (5-year OS 82.9% in Hi-FCR vs. 79.9% in Hi-W&W, p = 0.864). In conclusion, although FCR is efficient to induce remissions in the Binet A high-risk CLL, our data do not provide evidence that alters the current standard of care "watch and wait" for these patients.

中文翻译：

---

Binet分期患者的FCR早期治疗与观察和等待治疗的比较高风险的慢性淋巴细胞性白血病（CLL）：一项3期随机试验。

我们报告了一项随机前瞻性3期研究（CLL7），旨在评估氟达拉滨，环磷酰胺和利妥昔单抗（FCR）在早期高危慢性淋巴细胞性白血病（CLL）患者中的疗效。将800例未经治疗的Binet A病患者纳入意向性治疗人群，并评估四个预后指标：淋巴细胞加倍时间<12个月，血清胸苷激酶> 10 U / L，IGHV基因未突变和细胞遗传学不良（ del（11q）/ del（17p）/三体式12）。211位具有≥2个风险特征的患者被分类为高危CLL，并按1：1比例随机接受6xFCR立即治疗（Hi-FCR，100例患者）或根据护理标准进行观察（Hi- W＆W，101位患者）。早期FCR后的总缓解率为92.7％。常见的不良事件是血液学毒性和感染（分别占患者的61.0％/ 41.5％）。在中位观察时间为55.6（0-99.2）个月后，与Hi-W＆W患者相比，Hi-FCR的无事件生存期显着延长（中位数未达18.5个月，p <0.001）。对于接受早期FCR治疗的高危患者，没有显着的总体生存获益（Hi-FCR的5年OS为82.9％，而Hi-W＆W为79.9％，p = 0.864）。总之，尽管FCR可以有效地缓解Binet A高危CLL的症状，但我们的数据并未提供证据改变这些患者当前的“观察和等待”护理标准。与Hi-W＆W患者相比，Hi-FCR的无事件生存期显着延长（中位数未达18.5个月，p <0.001）。接受早期FCR治疗的高危患者没有明显的总体生存获益（Hi-FCR的5年OS为82.9％，而Hi-W＆W为79.9％，p = 0.864）。总之，尽管FCR可以有效地缓解Binet A高危CLL的症状，但我们的数据并未提供证据改变这些患者当前的“观察和等待”护理标准。与Hi-W＆W患者相比，Hi-FCR的无事件生存期显着延长（中位数未达18.5个月，p <0.001）。接受早期FCR治疗的高危患者没有明显的总体生存获益（Hi-FCR的5年OS为82.9％，而Hi-W＆W为79.9％，p = 0.864）。总之，尽管FCR可以有效地缓解Binet A高危CLL的症状，但我们的数据并未提供证据改变这些患者当前的“观察和等待”护理标准。