Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
N Engl J Med. 2012 Aug 9;367(6):520-31. doi: 10.1056/NEJMoa1200920.
The long-term prognosis for older patients with mantle-cell lymphoma is poor. Chemoimmunotherapy results in low rates of complete remission, and most patients have a relapse. We investigated whether a fludarabine-containing induction regimen improved the complete-remission rate and whether maintenance therapy with rituximab prolonged remission.
We randomly assigned patients 60 years of age or older with mantle-cell lymphoma, stage II to IV, who were not eligible for high-dose therapy to six cycles of rituximab, fludarabine, and cyclophosphamide (R-FC) every 28 days or to eight cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) every 21 days. Patients who had a response underwent a second randomization to maintenance therapy with rituximab or interferon alfa, each given until progression.
Of the 560 patients enrolled, 532 were included in the intention-to-treat analysis for response, and 485 in the primary analysis for response. The median age was 70 years. Although complete-remission rates were similar with R-FC and R-CHOP (40% and 34%, respectively; P=0.10), progressive disease was more frequent with R-FC (14%, vs. 5% with R-CHOP). Overall survival was significantly shorter with R-FC than with R-CHOP (4-year survival rate, 47% vs. 62%; P=0.005), and more patients in the R-FC group died during the first remission (10% vs. 4%). Hematologic toxic effects occurred more frequently in the R-FC group than in the R-CHOP group, but the frequency of grade 3 or 4 infections was balanced (17% and 14%, respectively). In 274 of the 316 patients who were randomly assigned to maintenance therapy, rituximab reduced the risk of progression or death by 45% (in remission after 4 years, 58%, vs. 29% with interferon alfa; hazard ratio for progression or death, 0.55; 95% confidence interval, 0.36 to 0.87; P=0.01). Among patients who had a response to R-CHOP, maintenance therapy with rituximab significantly improved overall survival (4-year survival rate, 87%, vs. 63% with interferon alfa; P=0.005).
R-CHOP induction followed by maintenance therapy with rituximab is effective for older patients with mantle-cell lymphoma. (Funded by the European Commission and others; ClinicalTrials.gov number, NCT00209209.).
老年套细胞淋巴瘤患者的长期预后较差。化疗联合免疫治疗的完全缓解率较低，大多数患者会复发。我们研究了氟达拉滨为基础的诱导方案是否能提高完全缓解率，以及利妥昔单抗维持治疗是否能延长缓解期。
我们将 60 岁及以上、不适合大剂量化疗的 II 期至 IV 期套细胞淋巴瘤患者随机分配至每 28 天接受 6 个周期利妥昔单抗、氟达拉滨和环磷酰胺（R-FC），或每 21 天接受 8 个周期利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松（R-CHOP）的治疗。有反应的患者进行第二次随机分组，分别接受利妥昔单抗或干扰素α维持治疗，直至疾病进展。
560 例患者中，532 例纳入意向治疗分析的缓解率，485 例纳入主要分析的缓解率。中位年龄为 70 岁。虽然 R-FC 和 R-CHOP 的完全缓解率相似（分别为 40%和 34%；P=0.10），但 R-FC 组的疾病进展更为常见（14%，而 R-CHOP 组为 5%）。R-FC 组的总生存时间明显短于 R-CHOP 组（4 年生存率为 47% vs. 62%；P=0.005），R-FC 组在首次缓解期间死亡的患者更多（10% vs. 4%）。R-FC 组比 R-CHOP 组更频繁发生血液学毒性反应，但 3 级或 4 级感染的发生率相当（分别为 17%和 14%）。在随机分配至维持治疗的 316 例患者中的 274 例中，利妥昔单抗使进展或死亡的风险降低了 45%（4 年后缓解率为 58%，而干扰素α组为 29%；进展或死亡的风险比为 0.55；95%置信区间为 0.36 至 0.87；P=0.01）。在对 R-CHOP 有反应的患者中，利妥昔单抗维持治疗显著提高了总生存时间（4 年生存率为 87%，而干扰素α组为 63%；P=0.005）。
R-CHOP 诱导后利妥昔单抗维持治疗对老年套细胞淋巴瘤患者有效。（由欧盟委员会和其他机构资助；临床试验注册号：NCT00209209.）。
