Hematology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin, Italy.
Hematology, Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino, Turin, Italy.
Lancet Oncol. 2014 Jun;15(7):730-7. doi: 10.1016/S1470-2045(14)70191-3. Epub 2014 May 13.
Up to 40% of elderly patients with untreated diffuse large B-cell lymphoma (DLBCL) given a regimen of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone every 21 days (R-CHOP21) relapse or develop refractory disease. Lenalidomide has high activity in relapsed or refractory aggressive B-cell lymphomas. In phase 2 of the REAL07 trial, we aimed to establish the safety and efficacy of the combination of lenalidomide and R-CHOP21 in elderly patients with untreated DLBCL.
REAL07 was an open-label, multicentre trial that was done in 13 centres in Italy and one in Germany. Eligible patients were aged 60-80 years; had newly diagnosed, untreated, CD20-positive, Ann Arbor stage II-IV DLBCL or grade 3b follicular lymphoma; had an Eastern Cooperative Oncology Group performance status of 0-2; had an International Prognostic Index (IPI) risk of low-intermediate, intermediate-high, or high; and were fit according to comprehensive geriatric assessment. Participants were to receive 15 mg oral lenalidomide on days 1-14 of six 21-day cycles, and standard doses of R-CHOP21 chemotherapy (375 mg/m(2) intravenous rituximab, 750 mg/m(2) intravenous cyclophosphamide, 50 mg/m(2) intravenous doxorubicin, and 1·4 mg/m(2) intravenous vincristine on day 1, and 40 mg/m(2) oral prednisone on days 1-5). The primary endpoint was frequency of overall response (complete response [CR] and partial response [PR]), which was assessed by (18)F-fluorodeoxyglucose ((18)F-FDG) PET at the end of the treatment. Analyses were by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00907348.
49 patients were included in phase 2: nine had been enrolled into phase 1 between Oct 23, 2008, and June 4, 2009, and had received the maximum tolerated dose of 15 mg lenalidomide; and 40 were enrolled into phase 2 between April 28, 2010, and June 3, 2011. 45 patients (92%, 95% CI 81-97) achieved a response (42 [86%] CR; three [6%] PR). Three patients (6%) did not respond and one (2%) died for reasons unrelated to treatment or disease. 277 (94%) of 294 planned cycles of lenalidomide and R-CHOP21 were completed. Grade 3-4 neutropenia was reported in 87 cycles (31%), grade 3-4 leukopenia in 77 (28%), and grade 3-4 thrombocytopenia in 35 (13%). No grade 4 non-haematological adverse events were reported. No patients died during the study as a result of toxic effects.
Lenalidomide with R-CHOP21 is effective and safe in elderly patients with untreated DLBCL.
Fondazione Italiana Linfomi and Celgene.
多达 40%未经治疗的弥漫性大 B 细胞淋巴瘤（DLBCL）老年患者接受利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松每 21 天（R-CHOP21）治疗后会复发或发展为难治性疾病。来那度胺在复发性或难治性侵袭性 B 细胞淋巴瘤中具有很高的活性。在 REAL07 试验的 2 期，我们旨在确定来那度胺联合 R-CHOP21 在未经治疗的 DLBCL 老年患者中的安全性和疗效。
REAL07 是一项开放标签、多中心试验，在意大利的 13 个中心和德国的 1 个中心进行。符合条件的患者年龄在 60-80 岁；新诊断为未经治疗的、CD20 阳性的、安阿伯分期 II-IV 期 DLBCL 或 3b 级滤泡淋巴瘤；东部合作肿瘤学组（ECOG）表现状态为 0-2；国际预后指数（IPI）风险为低-中、中-高或高；根据全面老年评估适合治疗。患者需接受 6 个 21 天周期中 15mg 口服来那度胺（第 1-14 天），并接受标准剂量的 R-CHOP21 化疗（第 1 天静脉注射 375mg/m2 利妥昔单抗、750mg/m2 环磷酰胺、50mg/m2 多柔比星和 1.4mg/m2 长春新碱，第 1-5 天口服 40mg/m2 泼尼松）。主要终点是总反应（完全缓解[CR]和部分缓解[PR]）的频率，这是通过治疗结束时（18）F-氟脱氧葡萄糖（（18）F-FDG）PET 评估的。分析是根据意向治疗进行的。这项试验在 ClinicalTrials.gov 注册，编号为 NCT00907348。
49 例患者入组 2 期：9 例于 2008 年 10 月 23 日至 2009 年 6 月 4 日入组 1 期，接受了 15mg 来那度胺的最大耐受剂量；40 例于 2010 年 4 月 28 日至 2011 年 6 月 3 日入组 2 期。45 例患者（92%，95%CI 81-97）达到了反应（42 例[86%]CR；3 例[6%]PR）。3 例（6%）未应答，1 例（2%）因与治疗或疾病无关的原因死亡。277 例（94%）计划的来那度胺和 R-CHOP21 周期完成。87 例（31%）报告出现 3-4 级中性粒细胞减少症，77 例（28%）报告出现 3-4 级白细胞减少症，35 例（13%）报告出现 3-4 级血小板减少症。未报告 4 级非血液学不良事件。没有患者因毒性作用在研究期间死亡。
来那度胺联合 R-CHOP21 治疗未经治疗的 DLBCL 老年患者是有效且安全的。
意大利淋巴瘤基金会和 Celgene。
