用 dexamethasone、利妥昔单抗和环磷酰胺对 Waldenström 巨球蛋白血症进行初始治疗。

Primary treatment of Waldenström macroglobulinemia with dexamethasone, rituximab, and cyclophosphamide.

作者信息

Dimopoulos Meletios Athanasios, Anagnostopoulos Athanasios, Kyrtsonis Marie-Christine, Zervas Konstantinos, Tsatalas Constantinos, Kokkinis Garyfallia, Repoussis Panagiotis, Symeonidis Argyris, Delimpasi Souzana, Katodritou Eirini, Vervessou Elina, Michali Evridiki, Pouli Anastasia, Gika Dimitra, Vassou Amalia, Terpos Evangelos, Anagnostopoulos Nikolaos, Economopoulos Theophanis, Pangalis Gerasimos

机构信息

Department of Clinical Therapeutics, University of Athens School of Medicine, Athens, Greece.

出版信息

J Clin Oncol. 2007 Aug 1;25(22):3344-9. doi: 10.1200/JCO.2007.10.9926. Epub 2007 Jun 18.

DOI:10.1200/JCO.2007.10.9926

PMID:17577016

Abstract

PURPOSE

Alkylating agents and the anti-CD20 monoclonal antibody rituximab are among appropriate choices for the primary treatment of symptomatic patients with Waldenström macroglobulinemia (WM), and they induce at least a partial response in 30% to 50% of patients. To improve these results, we designed a phase II study that included previously untreated symptomatic patients with WM who received a combination of dexamethasone, rituximab, and cyclophosphamide (DRC).

PATIENTS AND METHODS

Seventy-two patients were treated with dexamethasone 20 mg intravenously followed by rituximab 375 mg/m2 intravenously on day 1 and cyclophosphamide 100 mg/m2 orally bid on days 1 to 5 (total dose, 1,000 mg/m2). This regimen was repeated every 21 days for 6 months. Patients' median age was 69 years and many had features of advanced disease such as anemia (57%), hypoalbuminemia (40%), and elevated serum beta2-microglobulin (43%).

RESULTS

On an intent-to-treat basis, 83% of patients (95% CI, 73% to 91%) achieved a response, including 7% complete, 67% partial, and 9% minor responses. The median time to response was 4.1 months. The 2-year progression-free survival rate for all patients was 67%; for patients who responded to DRC, it was 80%. The 2-year disease-specific survival rate was 90%. Treatment with DRC was well tolerated, with 9% of patients experiencing grade 3 or 4 neutropenia and approximately 20% of patients experiencing some form of toxicity related to rituximab.

CONCLUSION

Our large, multicenter trial showed that the non-stem-cell toxic DRC regimen is an active, well-tolerated treatment for symptomatic patients with WM.

摘要

目的

烷化剂和抗CD20单克隆抗体利妥昔单抗是有症状的华氏巨球蛋白血症（WM）患者初始治疗的合适选择，它们可使30%至50%的患者至少获得部分缓解。为改善这些结果，我们设计了一项II期研究，纳入既往未接受治疗的有症状WM患者，给予地塞米松、利妥昔单抗和环磷酰胺（DRC）联合治疗。

患者与方法

72例患者接受静脉注射20mg地塞米松，第1天静脉注射375mg/m²利妥昔单抗，第1至5天口服环磷酰胺100mg/m²，每日2次（总剂量1000mg/m²）。每21天重复该方案，共6个月。患者的中位年龄为69岁，许多患者有晚期疾病特征，如贫血（57%）、低白蛋白血症（40%）和血清β2微球蛋白升高（43%）。

结果

在意向性治疗分析中，83%的患者（95%CI，73%至91%）获得缓解，包括7%完全缓解、67%部分缓解和9%轻微缓解。中位缓解时间为4.1个月。所有患者的2年无进展生存率为67%；对DRC有反应的患者为80%。2年疾病特异性生存率为90%。DRC治疗耐受性良好，9%的患者出现3或4级中性粒细胞减少，约20%的患者出现某种形式的与利妥昔单抗相关的毒性反应。