Rituximab, bendamustine, and lenalidomide in patients with aggressive B cell lymphoma not eligible for high-dose chemotherapy or anthracycline-based therapy: phase I results of the SAKK 38/08 trial
Rituximab, bendamustine, and lenalidomide in patients with aggressive B cell lymphoma not eligible for high-dose chemotherapy or anthracycline-based therapy: phase I results of the SAKK 38/08 trial
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DOI：
10.1007/s00277-013-1751-z
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发表时间：
2013-08-01
影响因子：
3.5
通讯作者：
Mey, U.
中科院分区：
文献类型：
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作者：
Hitz, F.;Fischer, N.;Mey, U.
这项I期试验旨在为不适合一线蒽环类药物化疗或积极二线治疗策略的侵袭性B细胞淋巴瘤患者开发一种新的有效且耐受性良好的方案。利妥昔单抗（375 mg/m2，第1天）、苯达莫司汀（70 mg/m2，第1天和第2天）和来那度胺的联合治疗采用3 + 3设计，来那度胺剂量递增至3个剂量水平（10、15或20 mg/天）。每4周重复一次课程。推荐剂量定义为低于剂量水平的一个水平，该剂量水平确定了在第一个周期内具有剂量限制性毒性（DLT）的千分之二/6患者。13例患者符合分析条件。中位年龄为77岁。12例患者的WHO体能状态为0或1。Charlson合并症指数显示所有患者均存在相关合并症。在第一个周期内，第二个剂量水平（15 mg/天）发生了2例DLT：1例患者发生了长期3级中性粒细胞减少症，1例患者发生了4级心脏不良事件（心肌梗死）。其他3级和4级毒性如下：中性粒细胞减少症（31%）、血小板减少症（23%）、心脏毒性（31%）、疲劳（15%）和皮疹（15%）。在随后的II期研究中，推荐来那度胺剂量为10 mg/天，第1天联合利妥昔单抗375 mg/m2，第1天和第2天联合苯达莫司汀70 mg/m2。
This phase I trial was designed to develop a new effective and well-tolerated regimen for patients with aggressive B cell lymphoma not eligible for front-line anthracycline-based chemotherapy or aggressive second-line treatment strategies. The combination of rituximab (375 mg/m(2) on day 1), bendamustine (70 mg/m(2) on days 1 and 2), and lenalidomide was tested with a dose escalation of lenalidomide at three dose levels (10, 15, or 20 mg/day) using a 3 + 3 design. Courses were repeated every 4 weeks. The recommended dose was defined as one level below the dose level identifying a parts per thousand yen2/6 patients with a dose-limiting toxicity (DLT) during the first cycle. Thirteen patients were eligible for analysis. Median age was 77 years. WHO performance status was 0 or 1 in 12 patients. The Charlson Comorbidity Index showed relevant comorbidities in all patients. Two DLTs occurred at the second dose level (15 mg/day) within the first cycle: one patient had prolonged grade 3 neutropenia, and one patient experienced grade 4 cardiac adverse event (myocardial infarction). Additional grade 3 and 4 toxicities were as follows: neutropenia (31 %), thrombocytopenia (23 %), cardiac toxicity (31 %), fatigue (15 %), and rash (15 %). The dose of lenalidomide of 10 mg/day was recommended for a subsequent phase II in combination with rituximab 375 mg/m(2) on day 1 and bendamustine 70 mg/m(2) on days 1 and 2.