Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study.
Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study.
复制标题
DOI：
10.1016/s1470-2045(11)70062-6
复制
发表时间：
2011-04
期刊：
影响因子：
51.1
通讯作者：
Witzig, Thomas E.
中科院分区：
文献类型：
--
作者：
Ansell, Stephen M.;Tang, Hui;Kurtin, Paul J.;Koenig, Patricia A.;Inwards, David J.;Shah, Keith;Ziesmer, Steven C.;Feldman, Andrew L.;Rao, Radha;Gupta, Mamta;Erlichman, Charles;Witzig, Thomas E.
替西罗莫司是一种mTOR抑制剂，在套细胞淋巴瘤（MCL）患者中具有单药抗肿瘤活性。因此，我们测试了替西罗莫司与利妥昔单抗联合治疗复发性或难治性MCL患者的疗效和毒性。患者在研究期间每周静脉注射替西罗莫司25 mg。在第一个周期中给予每周4次剂量的利妥昔单抗375 mg/m2，随后每隔28天周期给予单次剂量的利妥昔单抗。6个周期后有反应的患者可以继续治疗共12个周期，然后观察，无需额外的维持治疗。主要终点是利妥昔单抗敏感或利妥昔单抗难治性疾病患者中部分缓解或更好的比例。对所有接受治疗的患者进行了分析。该研究注册于ClinicalTrials.gov，编号NCT 00109967。2005年5月至2009年3月期间入组了71例患者。69例患者可评价并纳入最终分析。患者既往接受过中位两种治疗（范围1-9），30.4%（21/69）既往接受过干细胞移植，30.4%（21/69）为利妥昔单抗难治性。总缓解率（ORR）为59.4%（41/69例患者），其中18.8%（13/69例）完全缓解，40.6%（28/69例）部分缓解。利妥昔单抗敏感患者的ORR为62.5%（30/48; 95% CI 47.4 - 76.1%），利妥昔单抗难治患者的ORR为52.4%（11/21; 95% CI 29.8 - 74.3%）。最常见的治疗相关3-4级不良事件为16例患者（23.2%）的血小板减少症、15例患者（21.7%）的中性粒细胞减少症、10例患者（14.5%）的疲乏、7例患者（10.1%）的肺炎、7例患者（10.1%）的淋巴细胞减少症、5例患者（7.2%）的肺炎、5例患者（7.2%）的呼吸困难和5例患者（7.2%）的高血糖症。mTOR抑制剂联合利妥昔单抗可能在治疗复发性和难治性MCL患者中发挥作用。
Temsirolimus is an mTOR inhibitor with single-agent antitumor activity in patients with mantle cell lymphoma (MCL). We therefore tested the efficacy and toxicity of temsirolimus in combination with rituximab in patients with relapsed or refractory MCL. Patients received temsirolimus 25 mg intravenously weekly while on study. Four weekly doses of rituximab 375mg/m2 were given during the first cycle followed by a single dose of rituximab every other 28-day cycle thereafter. Responding patients after six cycles could continue treatment for a total of 12 cycles and were then observed without additional maintenance therapy. The primary endpoint was the proportion of patients with either rituximab-sensitive or rituximab-refractory disease who had a partial response or better. The analyses were done on all patients who received treatment. The study was registered with ClinicalTrials.gov, number NCT00109967. Seventy-one patients were enrolled between May 2005 and March 2009. Sixty-nine patients are evaluable and are included in the final analysis. Patients had received a median of two prior therapies (range, 1-9), 30·4% (21/69) had received a prior stem cell transplant and 30·4% (21/69) were rituximab-refractory. The overall response rate (ORR) was 59·4% (41/69 patients) with 18·8% (13/69) complete responses and 40·6% (28/69) partial responses. The ORR for rituximab-sensitive patients was 62·5% (30/48; 95% CI 47·4-76·1%) and 52·4% (11/21; 95% CI 29·8 – 74·3%) for rituximab-refractory patients. The most common treatment-related grade 3-4 adverse events were thrombocytopenia in 16 patients (23·2%), neutropenia in 15 (21·7%), fatigue in 10 (14·5%), pneumonia in 7 (10·1%), lymphopenia in 7 (10·1%), pneumonitis in 5 (7·2%), dyspnea in 5 (7·2%) and hypertriglyceridemia in 5 (7·2%). mTOR inhibitors in combination with rituximab could have a role in the treatment of patients with relapsed and refractory MCL.