Habermann Thomas M, Weller Edie A, Morrison Vicki A, Gascoyne Randy D, Cassileth Peter A, Cohn Jeffrey B, Dakhil Shaker R, Woda Bruce, Fisher Richard I, Peterson Bruce A, Horning Sandra J
Division of Hematology, Mayo Clinic, 200 First St SW, Rochester, MN 55905, USA.
J Clin Oncol. 2006 Jul 1;24(19):3121-7. doi: 10.1200/JCO.2005.05.1003. Epub 2006 Jun 5.
To address early and late treatment failures in older patients with diffuse large B-cell lymphoma (DLBCL), we designed a two-stage randomized trial of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) versus rituximab plus CHOP (R-CHOP), with a second random assignment to maintenance rituximab (MR) or observation in responding patients.
Untreated DLBCL patients who were 60 years or older were randomly assigned to R-CHOP (n = 318) or CHOP (n = 314); 415 responders were randomly assigned to MR (n = 207) or observation (n = 208). The primary end point was failure-free survival (FFS). All P values were two sided.
Three-year FFS rate was 53% for R-CHOP patients and 46% for CHOP patients (P = .04) at a median follow-up time of 3.5 years. Two-year FFS rate from second random assignment was 76% for MR compared with 61% for observation (P = .009). No significant differences in survival were seen according to induction or maintenance therapy. FFS was prolonged with MR after CHOP (P = .0004) but not after R-CHOP (P = .81) with 2-year FFS rates from second random assignment of 77%, 79%, 74%, and 45% for R-CHOP, R-CHOP + MR, CHOP + MR, and CHOP, respectively. In a secondary analysis excluding MR patients, R-CHOP alone reduced the risks of treatment failure (P = .003) and death (P = .05) compared with CHOP alone.
Rituximab administered as induction or maintenance with CHOP chemotherapy significantly prolonged FFS in older DLBCL patients. After R-CHOP, no benefit was provided by MR. These results, which are consistent with an additive effect of rituximab, suggest that future studies could focus on maintenance strategies with novel agents as well as new induction therapies.
为解决老年弥漫性大B细胞淋巴瘤（DLBCL）患者早期和晚期治疗失败的问题，我们设计了一项两阶段随机试验，比较环磷酰胺、阿霉素、长春新碱和泼尼松（CHOP）方案与利妥昔单抗联合CHOP（R-CHOP）方案，对缓解患者再随机分为接受利妥昔单抗维持治疗（MR）或观察。
年龄60岁及以上的初治DLBCL患者被随机分为R-CHOP组（n = 318）或CHOP组（n = 314）；415例缓解患者被随机分为MR组（n = 207）或观察组（n = 208）。主要终点是无失败生存期（FFS）。所有P值均为双侧。
在中位随访时间3.5年时，R-CHOP组患者的3年FFS率为53%，CHOP组为46%（P = .04）。第二次随机分组后的2年FFS率，MR组为76%，观察组为61%（P = .009）。根据诱导或维持治疗，生存率无显著差异。CHOP方案后接受MR治疗可延长FFS（P = .0004），但R-CHOP方案后则不然（P = .81），第二次随机分组后的2年FFS率，R-CHOP组、R-CHOP + MR组、CHOP + MR组和CHOP组分别为77%、79%、74%和45%。在一项排除MR患者的二次分析中，与单纯CHOP相比，单纯R-CHOP降低了治疗失败风险（P = .003）和死亡风险（P = .05）。
利妥昔单抗与CHOP化疗联合作为诱导或维持治疗可显著延长老年DLBCL患者的FFS。R-CHOP方案后，MR无获益。这些结果与利妥昔单抗的相加作用一致，表明未来研究可聚焦于新型药物的维持策略以及新的诱导治疗。
