PURPOSE In an update of the randomized, open-label, phase III European Mantle Cell Lymphoma (MCL) Elderly trial (ClinicalTrials.gov identifier: NCT00209209), published in 2012, we aimed to confirm results on long-term outcome focusing on efficacy and safety of long-term use of rituximab maintenance. PATIENTS AND METHODS Five hundred sixty patients with newly diagnosed MCL underwent a first random assignment between rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and rituximab, fludarabine, and cyclophosphamide (R-FC) induction, followed by a second random assignment in 316 responders between rituximab and interferon alfa maintenance, to be continued until progression. We compared progression-free survival from the second randomization and overall survival (OS) from the first or second randomizations. RESULTS After a median follow-up time of 7.6 years, the previously described difference in OS between the induction arms persisted (median, 6.4 years after R-CHOP [n = 280] v 3.9 years after R-FC [n = 280]; P = .0054). Patients responding to R-CHOP had median progression-free survival and OS times of 5.4 and 9.8 years, respectively, when randomly assigned to rituximab (n = 87), compared with 1.9 years (P < .001) and 7.1 years (P = .0026), respectively, when randomly assigned to interferon alfa (n = 97). In 58% and 32% of patients treated with R-CHOP, rituximab maintenance was still ongoing 2 and 5 years from start of maintenance, respectively. After R-FC, rituximab maintenance was associated with an unexpectedly high cumulative incidence of death in remission (22% at 5 years). Toxicity of rituximab maintenance was low after R-CHOP (grade 3-4 leukopenia or infection < 5%) but more prominent in patients on rituximab maintenance after R-FC, in whom grade 3-4 leukopenia (up to 40%) and infections were frequent (up to 15%). CONCLUSION The excellent results of R-CHOP followed by rituximab maintenance until progression for older patients with MCL persisted in a mature follow-up. Prolongation of rituximab maintenance beyond 2 years is effective and safe.

中文翻译：

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套细胞淋巴瘤 (MCL) 老年患者的治疗：欧洲 MCL 老年随机试验的长期随访

目的 在 2012 年发表的随机、开放标签、III 期欧洲套细胞淋巴瘤 (MCL) 老年人试验（ClinicalTrials.gov 标识符：NCT00209209）的更新中，我们旨在确认长期结果的结果，重点是疗效和长期使用利妥昔单抗的安全性维护。患者和方法 560 名新诊断的 MCL 患者接受了利妥昔单抗、环磷酰胺、多柔比星、长春新碱和强的松 (R-CHOP) 和利妥昔单抗、氟达拉滨和环磷酰胺 (R-FC) 诱导之间的第一次随机分配，然后进行了第二次诱导在 316 名应答者中随机分配利妥昔单抗和干扰素 alfa 维持治疗，直至进展。我们比较了第二次随机分组的无进展生存期和第一次或第二次随机分组的总生存期 (OS)。结果 中位随访时间为 7.6 年后，先前描述的诱导组之间的 OS 差异仍然存在（中位数，R-CHOP 后 6.4 年 [n = 280] v R-FC 后 3.9 年 [n = 280]； P = .0054）。当随机分配到利妥昔单抗组 (n = 87) 时，对 R-CHOP 有反应的患者的中位无进展生存期和 OS 时间分别为 5.4 年和 9.8 年，而分别为 1.9 年 (P < .001) 和 7.1 年 (P = .0026)，当随机分配给干扰素 alfa (n = 97) 时。在接受 R-CHOP 治疗的患者中，分别有 58% 和 32% 的患者在维持治疗开始后 2 年和 5 年仍继续维持利妥昔单抗。R-FC 后，利妥昔单抗维持治疗与出乎意料的高缓解期累积死亡发生率相关（5 年时为 22%）。R-CHOP 后利妥昔单抗维持的毒性较低（3-4 级白细胞减少或感染 < 5%），但在 R-FC 后接受利妥昔单抗维持的患者中更为突出，其中 3-4 级白细胞减少（高达 40%）和感染频繁（高达 15%）。结论 对于老年 MCL 患者，R-CHOP 继以利妥昔单抗维持直至进展的优异结果在成熟的随访中持续存在。延长 rituximab 维持时间超过 2 年是有效且安全的。