Department of Internal Medicine III (Hematology, Oncology, Pneumology), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
III. Medical Department, Technical University Munich, Munich, Germany.
Leukemia. 2015 Aug;29(8):1695-701. doi: 10.1038/leu.2015.60. Epub 2015 Mar 13.
In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with r/r follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1-3 prior therapies received Bendamustine (90 mg/m(2), day 1+2) and Rituximab (375 mg/m(2), day 1) with Temsirolimus in doses from 25 to 75 mg added on day 1, 8, 15 of a 28-day cycle. Fifteen (11 MCL, 4 FL) patients were included in the phase I. Median age was 73 years and median pretreatment number was 2. No formal dose-limiting toxicity was observed. Dominant non-hematological side effects were fatigue in 11 (73%), nausea in 9 (60%), mucositis in 7 (47%) and vomiting in 6 patients (40%). Cough, diarrhea, pyrexia and rash were observed in five patients (33%) each. Grade 3/4 events included leukopenia in 6 (40%), neutropenia in 4 (27%) and thrombocytopenia in 2 patients (13%). An objective response was observed in 14/15 patients (93%), including 5 complete response (33%; all MCL). After a median follow-up of 19 months, 67% of patients are without signs of progression. Temsirolimus can be safely added to BR with promising preliminary activity. Recruitment in phase II is ongoing.
在这项 I/II 期研究中，我们探索了替西罗莫司联合苯达莫司汀和利妥昔单抗（BeRT）治疗复发/难治性滤泡淋巴瘤（FL）或套细胞淋巴瘤（MCL）患者的疗效。既往接受过 1-3 线治疗的患者接受苯达莫司汀（90mg/m2，第 1+2 天）和利妥昔单抗（375mg/m2，第 1 天），替西罗莫司剂量为 25-75mg，于第 1、8、15 天加入，每 28 天为一个周期。15 例（11 例 MCL，4 例 FL）患者入组 I 期。中位年龄为 73 岁，中位预处理数量为 2 个。未观察到明确的剂量限制毒性。主要的非血液学不良反应是 11 例（73%）疲劳、9 例（60%）恶心、7 例（47%）黏膜炎和 6 例（40%）呕吐。咳嗽、腹泻、发热和皮疹各有 5 例（33%）。3/4 级事件包括 6 例（40%）白细胞减少、4 例（27%）中性粒细胞减少和 2 例（13%）血小板减少。15 例患者中观察到 14 例（93%）客观缓解，包括 5 例完全缓解（33%；均为 MCL）。中位随访 19 个月后，67%的患者无疾病进展迹象。替西罗莫司联合 BR 治疗具有较好的安全性和初步疗效，目前正在进行 II 期临床试验。
