替西罗莫司和利妥昔单抗治疗复发或难治性套细胞淋巴瘤患者：一项 2 期研究。
Temsirolimus and rituximab in patients with relapsed or refractory mantle cell lymphoma: a phase 2 study.
机构信息
Division of Hematology, Mayo Clinic, Rochester, MN 55905, USA.
出版信息
Lancet Oncol. 2011 Apr;12(4):361-8. doi: 10.1016/S1470-2045(11)70062-6.
BACKGROUND
Temsirolimus is a mammalian target of rapamycin (mTOR) inhibitor with single-agent antitumour activity in patients with mantle cell lymphoma. We therefore tested its efficacy and toxicity in combination with rituximab (an antiCD20 antibody) in patients with relapsed or refractory mantle cell lymphoma.
METHODS
In a phase 2 study, patients (aged ≥18 years) at 35 centres in the USA were given temsirolimus 25 mg/week, and rituximab 375 mg/m(2) per week for 4 weeks during the first cycle and thereafter a single dose of rituximab every other 28-day cycle. Both drugs were administered intravenously. Responding patients after six cycles could continue treatment for a total of 12 cycles, and were then observed without additional maintenance treatment. The primary endpoint was the proportion of patients with either rituximab-sensitive or rituximab-refractory disease who had at least a partial response. The analyses were done on all patients who were treated. The study was registered with ClinicalTrials.gov, number NCT00109967.
FINDINGS
71 patients with mantle cell lymphoma were enrolled and 69 were assessable and were included in the final analysis. The overall response rate (ORR) was 59% (41 of 69 patients)-13 (19%) patients had complete responses and 28 (41%) had partial responses. The ORR was 63% (30 of 48; 95% CI 47-76) for rituximab-sensitive patients, and 52% (11 of 21; 30-74) for rituximab-refractory patients. The most common treatment-related grade 3 or 4 adverse events in rituximab-sensitive and rituximab-refractory patients were thrombocytopenia (eight [17%] and eight [38%], respectively), neutropenia (ten [21%] and five [24%], respectively), fatigue (eight [17%] and two [10%], respectively), leucopenia (six [13%] and three [14%], respectively), pneumonia (five [10%] and two [10%], respectively), lymphopenia (five [10%] and two [10%], respectively), pneumonitis (four [8%] and none, respectively), oedema (four [8%] and none, respectively), dyspnoea (three [6%] and two [10%], respectively), and hypertriglyceridaemia (three [6%] and two [10%], respectively).
INTERPRETATION
mTOR inhibitors in combination with rituximab could have a role in the treatment of patients with relapsed and refractory mantle cell lymphoma.
FUNDING
National Institutes of Health and the Predolin Foundation.
背景
替西罗莫司是一种哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂，在套细胞淋巴瘤患者中具有单药抗肿瘤活性。因此，我们在复发或难治性套细胞淋巴瘤患者中测试了其与利妥昔单抗（一种抗 CD20 抗体）联合使用的疗效和毒性。
方法
在一项 2 期研究中，美国 35 个中心的患者（年龄≥18 岁）接受每周 25 毫克替西罗莫司和每周 375 毫克/平方米利妥昔单抗，在第一个周期的 4 周内进行，此后每 28 天周期给予单次利妥昔单抗剂量。两种药物均通过静脉输注。在 6 个周期后有应答的患者可以继续接受总共 12 个周期的治疗，然后在没有额外维持治疗的情况下进行观察。主要终点是至少有部分缓解的利妥昔单抗敏感或利妥昔单抗耐药疾病患者的比例。所有接受治疗的患者均进行了分析。该研究在 ClinicalTrials.gov 上注册，编号为 NCT00109967。
结果
共纳入 71 例套细胞淋巴瘤患者，69 例可评估，纳入最终分析。总缓解率（ORR）为 59%（69 例患者中有 41 例）-13 例（19%）患者完全缓解，28 例（41%）患者部分缓解。利妥昔单抗敏感患者的 ORR 为 63%（30 例，95%CI 47-76），利妥昔单抗耐药患者的 ORR 为 52%（11 例，30-74）。利妥昔单抗敏感和利妥昔单抗耐药患者最常见的与治疗相关的 3 级或 4 级不良事件为血小板减少症（分别为 8 [17%]和 8 [38%]）、中性粒细胞减少症（分别为 10 [21%]和 5 [24%]）、疲劳（分别为 8 [17%]和 2 [10%]）、白细胞减少症（分别为 6 [13%]和 3 [14%]）、肺炎（分别为 5 [10%]和 2 [10%]）、淋巴细胞减少症（分别为 5 [10%]和 2 [10%]）、肺炎（分别为 4 [8%]和无，分别）、水肿（分别为 4 [8%]和无，分别）、呼吸困难（分别为 3 [6%]和 2 [10%]）和高甘油三酯血症（分别为 3 [6%]和 2 [10%]）。
解释
mTOR 抑制剂联合利妥昔单抗可能在治疗复发和难治性套细胞淋巴瘤患者方面发挥作用。
资金来源
美国国立卫生研究院和 Predolin 基金会。
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