利妥昔单抗治疗弥漫性大 B 细胞淋巴瘤的优化（二）：德国高级非霍奇金淋巴瘤研究组 SMARTE-R-CHOP-14 试验中延长利妥昔单抗暴露时间。
Optimization of rituximab for the treatment of diffuse large B-cell lymphoma (II): extended rituximab exposure time in the SMARTE-R-CHOP-14 trial of the german high-grade non-Hodgkin lymphoma study group.
机构信息
Michael Pfreundschuh, Viola Poeschel, Gerhard Held, Tanja Rixecker, Carsten Zwick, and Niels Murawski, Universitätsklinikum des Saarlandes, Homburg; Samira Zeynalova, Leipzig University, Leipzig; Mathias Hänel, Klinikum Chemnitz, Chemnitz; Norbert Schmitz, Asklepios Klinik St Georg, Hamburg; Andreas Viardot, Universitätsklinikum Ulm, Ulm; Martin H. Dreyling, Klinikum Großhadern; Ulrich Keller, Klinikum Rechts der Isar, Munich; Michael Hallek, Carsten Mueller, and Martin H.J. Wiesen, Universitätsklinik Köln, Köln; Mathias Witzens-Harig, Universitätsklinik Heidelberg, Heidelberg; and Lorenz Truemper, Universitätsklinikum Göttingen, Göttingen, Germany.
出版信息
J Clin Oncol. 2014 Dec 20;32(36):4127-33. doi: 10.1200/JCO.2013.54.6861. Epub 2014 Nov 17.
PURPOSE
To study pharmacokinetics, toxicity, and efficacy of prolonged rituximab exposure in elderly patients with diffuse large B-cell lymphoma (DLBCL).
PATIENTS AND METHODS
In the SMARTE-R-CHOP-14 trial, rituximab 375 mg/m(2) was administered, together with six cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone on a 14-day schedule (6×R-CHOP-14), on days -4, 0, 10, 29, 57, 99, 155, and 239. Pharmacokinetics and outcome were to be compared with those of patients who had received 6×R-CHOP-14 in combination with eight 2-week applications of rituximab in the RICOVER-60 (Rituximab With CHOP Over Age 60 Years) trial.
RESULTS
The complete response (CR)/unconfirmed CR rate was 85% in 189 evaluable patients, 90% for 90 good-prognosis patients (International Prognostic Index [IPI], 1 or 2), and 81% for 99 poor-prognosis patients (IPI, 3 to 5); 3-year event-free survival (EFS) was 71%, 75%, and 67%, respectively; and 3-year overall survival (OS) was 84%, 88%, and 80%, respectively, with no differences between men and women. The preplanned historical comparison with 306 RICOVER-60 patients (good prognosis, n = 183; poor prognosis, n = 123) revealed no outcome differences for all and good-prognosis patients; however, the longer exposure time in SMARTE-R-CHOP-14 compared with RICOVER-60 was associated with better 3-year EFS (67% v 54%) and OS (80% v 67%) in poor-prognosis patients.
CONCLUSION
Extended rituximab exposure compared with eight 2-week applications in combination with 6×R-CHOP-14 significantly improved outcome of elderly poor-prognosis patients without increasing toxicity. To our knowledge, results obtained with the SMARTE-R-CHOP-14 rituximab schedule are the best reported for elderly patients with DLBCL to date. In the subgroup of poor-prognosis patients treated with extended rituximab exposure, the outcome seemed superior to that of a similar historical cohort of patients treated with 6×R-CHOP-14 plus 2-week rituximab, with similar toxicity. A randomized comparison of the two schedules is warranted.
目的
研究延长利妥昔单抗暴露时间对老年弥漫性大 B 细胞淋巴瘤（DLBCL）患者的药代动力学、毒性和疗效。
方法
在 SMARTE-R-CHOP-14 试验中，给予利妥昔单抗 375mg/m²，与六周期利妥昔单抗联合环磷酰胺、多柔比星、长春新碱和泼尼松在 14 天的方案（6×R-CHOP-14），于-4、0、10、29、57、99、155 和 239 天给药。药代动力学和结果将与 RICOVER-60 试验中接受 6×R-CHOP-14 联合 8 个 2 周应用利妥昔单抗的患者进行比较。
结果
189 例可评估患者的完全缓解（CR）/未确认 CR 率为 85%，90 例预后良好患者（国际预后指数[IPI]，1 或 2）为 90%，99 例预后不良患者（IPI，3-5）为 81%；3 年无事件生存（EFS）分别为 71%、75%和 67%；3 年总生存（OS）分别为 84%、88%和 80%，男女之间无差异。与 306 例 RICOVER-60 患者（预后良好，n=183；预后不良，n=123）的预先计划的历史比较显示，所有患者和预后良好患者的结果无差异；然而，与 RICOVER-60 相比，SMARTE-R-CHOP-14 的更长暴露时间与预后不良患者的 3 年 EFS（67%比 54%）和 OS（80%比 67%）更好相关。
结论
与 6×R-CHOP-14 联合 8 个 2 周应用相比，延长利妥昔单抗暴露时间显著改善了老年预后不良患者的预后，而不增加毒性。据我们所知，SMARTE-R-CHOP-14 利妥昔单抗方案的结果是迄今为止老年 DLBCL 患者的最佳报道。在接受延长利妥昔单抗暴露治疗的预后不良亚组患者中，结果似乎优于接受 6×R-CHOP-14 加 2 周利妥昔单抗治疗的类似历史队列患者，且毒性相似。需要对两种方案进行随机比较。
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