Department of Hematology, Copernicus Memorial Hospital, Medical University of Lodz, Lodz, Poland.
Department of Hematology, Jagiellonian University, Kraków, Poland.
Eur J Haematol. 2018 May;100(5):465-474. doi: 10.1111/ejh.13042. Epub 2018 Mar 22.
PALG CLL4 is the first, randomized, phase IIIb study with rituximab, cladribine, and cyclophosphamide (RCC) induction and subsequent maintenance with rituximab in previously untreated chronic lymphocytic leukemia (CLL) patients.
The induction treatment consisted of 6 RCC cycles regimen. Patients with complete response (CR) or partial response (PR) after an induction phase were randomized into a maintenance arm with rituximab or an observational arm.
In the intention-to-treat population, 97 patients completed the induction phase with an overall response rate (ORR) of 73.2% (CR 22.7%, PR 50.5%). Subsequently, 66 patients were randomized into the rituximab maintenance arm (n = 33) or the observational arm (n = 33). CR rates were 57.1% in the maintenance group vs 50% in the observational group. PFS was significantly longer in the rituximab maintenance vs the observational arm (P = .028). The multivariate Cox model indicated that del17p (P = .006) and elevated beta-2-microglobulin (P = .015) significantly increased the hazard ratio (HR) of progression, whereas the presence of CD38 (P = .013) significantly decreased it; maintenance therapy with rituximab (P < .0001) significantly decreased the HR of disease progression.
The study confirmed the high efficacy and acceptable safety profile of induction therapy with RCC and maintenance therapy with rituximab in previously untreated patients with CLL.
PALG CLL4 是第一项针对初治慢性淋巴细胞白血病（CLL）患者的利妥昔单抗、克拉屈滨和环磷酰胺（RCC）诱导及随后利妥昔单抗维持的随机、IIIb 期研究。
诱导治疗包括 6 个 RCC 周期方案。诱导阶段后达到完全缓解（CR）或部分缓解（PR）的患者被随机分为利妥昔单抗维持组或观察组。
在意向治疗人群中，97 例患者完成了诱导阶段，总缓解率（ORR）为 73.2%（CR 22.7%，PR 50.5%）。随后，66 例患者被随机分为利妥昔单抗维持组（n=33）或观察组（n=33）。维持组的 CR 率为 57.1%，观察组为 50%。利妥昔单抗维持组的无进展生存期（PFS）显著长于观察组（P=0.028）。多变量 Cox 模型表明，del17p（P=0.006）和β2-微球蛋白升高（P=0.015）显著增加了进展的风险比（HR），而 CD38 的存在（P=0.013）显著降低了它；利妥昔单抗维持治疗（P<0.0001）显著降低了疾病进展的 HR。
该研究证实了 RCC 诱导治疗和利妥昔单抗维持治疗在初治 CLL 患者中的高疗效和可接受的安全性。
