Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi
Lenalidomide plus cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab is safe and effective in untreated, elderly patients with diffuse large B-cell lymphoma: a phase I study by the Fondazione Italiana Linfomi
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DOI：
10.3324/haematol.2013.085134
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发表时间：
2013-11-01
期刊：
影响因子：
10.1
通讯作者：
Vitolo, Umberto
中科院分区：
文献类型：
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作者：
Chiappella, Annalisa;Tucci, Alessandra;Vitolo, Umberto
尽管利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松的标准治疗对于未经治疗的弥漫性大 B 细胞淋巴瘤患者有所改善，但这些患者中高达 40% 的患者会复发。单独使用来那度胺或与利妥昔单抗联合使用已被证明对复发/难治性侵袭性淋巴瘤有效。在这项 I 期研究中，我们确定了来那度胺加利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松在未经治疗的老年（中位年龄 68 岁）弥漫性大 B 细胞淋巴瘤患者中的最大耐受剂量。使用持续重新评估方法分配的四剂来那度胺（第 1-14 天为 5、10、15 和 20 mg/天）计划与每个疗程的利妥昔单抗、环磷酰胺、阿霉素、长春新碱和泼尼松联合给药，为期 14 天，总共 6 个疗程。七组患者（每组 n=3）接受 10、20、15、15、15、10 和 10 mg 来那度胺治疗（总共 n=21）。在前三个疗程中，七名患者出现了剂量限制性毒性。选择来那度胺的第三个剂量水平（15 mg/天）作为最大耐受剂量，剂量限制毒性的估计概率为0.345（95%可信区间0.164-0.553）。 3-4级血液学不良事件为：28%的疗程出现中性粒细胞减少，9%出现血小板减少，3%出现贫血。非血液学毒性为中度：4 级肌酐磷酸激酶升高 (n=1)、3 级心脏毒性 (n=2)、3 级神经毒性 (n=3) 和 3 级胃肠道毒性 (n=1)。在这项 I 期研究中，总体缓解率为 90%，其中 81% 达到完全缓解。这种联合治疗方案对于患有弥漫性大 B 细胞淋巴瘤的老年患者来说似乎是安全的，其疗效将在正在进行的 II 期试验中进行评估。
Despite improvements in standard therapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone for patients with untreated, diffuse large B-cell lymphoma, up to 40% of these patients relapse. Lenalidomide alone or in combination with rituximab has been shown to be active in relapsed/refractory aggressive lymphomas. In this phase I study we determined the maximum tolerated dose of lenalidomide plus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone in untreated, elderly (median age 68 years) patients with diffuse large B-cell lymphoma. Four lenalidomide doses (5, 10, 15, and 20 mg/day on days 1-14) allocated using the continual reassessment method were planned to be administered for 14 days in combination with each course of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone for a total of six courses. Seven cohorts of patients (n=3 in each cohort) were treated (total n=21) at 10, 20, 15, 15, 15, 10, and 10 mg of lenalidomide. Dose-limiting toxicities occurred in seven patients during the first three courses of treatment. The third dose-level of lenalidomide (15 mg/day) was selected as the maximum tolerated dose, with an estimated probability of dose-limiting toxicities of 0.345 (95% credibility interval 0.164-0.553). Grade 3-4 hematologic adverse events were: neutropenia in 28% of the courses, thrombocytopenia in 9%, and anemia in 3%. Non-hematologic toxicities were moderate: grade 4 increase of creatinine phosphokinase (n=1), grade 3 cardiac (n=2), grade 3 neurological (n=3), and grade 3 gastrointestinal (n=1). In this phase I study, the overall response rate was 90%, with 81% achieving complete remission. This combination regimen appears safe in elderly patients with diffuse large B-cell lymphoma and its efficacy will be assessed in the ongoing phase II trial.