利妥昔单抗巩固和维持免疫疗法可改善B细胞慢性淋巴细胞白血病患者的临床结局。

Consolidation and maintenance immunotherapy with rituximab improve clinical outcome in patients with B-cell chronic lymphocytic leukemia.

作者信息

Del Poeta Giovanni, Del Principe Maria Ilaria, Buccisano Francesco, Maurillo Luca, Capelli Giovanni, Luciano Fabrizio, Perrotti Alessio Pio, Degan Massimo, Venditti Adriano, de Fabritiis Paolo, Gattei Valter, Amadori Sergio

机构信息

Department of Hematology, University Tor Vergata, S. Eugenio Hospital, Rome, Italy.

出版信息

Cancer. 2008 Jan 1;112(1):119-28. doi: 10.1002/cncr.23144.

DOI:10.1002/cncr.23144

PMID:17999417

Abstract

BACKGROUND

Rituximab in sequential combination with fludarabine (Flu) allowed patients with B-cell chronic lymphocytic leukemia (B-CLL) to achieve higher remission rates and longer response duration. Based on their recent experience in indolent non-Hodgkin lymphomas, in this study, the authors attempted to demonstrate whether consolidation/maintenance therapy with rituximab could prolong the response duration in this patient population.

METHODS

This Phase II study was based on a consolidation/maintenance therapy with rituximab for patients in complete remission (CR) or partial remission (PR) who were positive for minimal residual disease (MRD), as determined by flow cytometry. Seventy-five symptomatic, untreated patients with B-CLL received 6 monthly cycles of Flu (25 mg/m(2) for 5 days) followed by 4 weekly doses of rituximab (375 mg/m(2)). Then, 28 patients who were positive for MRD were consolidated with 4 monthly cycles of rituximab (375 mg/m(2)) followed by 12 monthly low doses of rituximab (150 mg/m(2)).

RESULTS

Based on National Cancer Institute criteria, 61 of 75 patients (81%) achieved a CR, 10 of 75 patients (13%) had a PR, and 4 of 75 patients (5%) had either no response or disease progression. MRD-positive patients in CR or PR who received consolidation therapy (n = 28 patients) had a significantly longer response duration (87% vs 32% at 5 years; P = .001) compared with a subset of patients who did not receive consolidation therapy (n = 18 patients). All patients experienced a long progression-free survival from the end of induction treatment (73% at 5 years). It was noteworthy that, within the subset of ZAP-70-positive patients, MRD-positive, consolidated patients (n = 12 patients) had a significantly longer response duration (69% vs 0% at 2.6 years; P = .007) compared with MRD-positive, unconsolidated patients (n = 11 patients).

CONCLUSIONS

The addition of a consolidation and maintenance therapy with rituximab prolonged response duration significantly in patients with MRD-positive B-CLL.

摘要

背景

利妥昔单抗与氟达拉滨（Flu）序贯联合使用可使B细胞慢性淋巴细胞白血病（B-CLL）患者获得更高的缓解率和更长的缓解持续时间。基于他们在惰性非霍奇金淋巴瘤方面的最新经验，在本研究中，作者试图证明利妥昔单抗巩固/维持治疗是否能延长该患者群体的缓解持续时间。

方法

本II期研究基于对通过流式细胞术确定为微小残留病（MRD）阳性的完全缓解（CR）或部分缓解（PR）患者进行利妥昔单抗巩固/维持治疗。75例有症状的未经治疗的B-CLL患者接受6个每月周期的Flu（25mg/m²，共5天），随后是4个每周剂量的利妥昔单抗（375mg/m²）。然后，28例MRD阳性患者接受4个每月周期的利妥昔单抗（375mg/m²）巩固治疗，随后是12个每月低剂量的利妥昔单抗（150mg/m²）。

结果

根据美国国立癌症研究所标准，75例患者中有61例（81%）达到CR，75例患者中有10例（13%）为PR，75例患者中有4例（5%）无反应或疾病进展。与未接受巩固治疗的一部分患者（n = 18例）相比，接受巩固治疗的CR或PR的MRD阳性患者（n = 28例）的缓解持续时间显著更长（5年时为87%对32%；P = 0.001）。所有患者从诱导治疗结束起均经历了较长的无进展生存期（5年时为73%）。值得注意的是，在ZAP-70阳性患者亚组中，与MRD阳性、未巩固治疗的患者（n = 11例）相比，MRD阳性、接受巩固治疗的患者（n = 12例）的缓解持续时间显著更长（2.6年时为69%对0%；P = 0.007）。