Ogura Michinori, Imaizumi Yoshitaka, Uike Naokuni, Asou Norio, Utsunomiya Atae, Uchida Toshiki, Aoki Tomohiro, Tsukasaki Kunihiro, Taguchi Jun, Choi Ilseung, Maruyama Dai, Nosaka Kisato, Chen Nianhang, Midorikawa Shuichi, Ohtsu Tomoko, Tobinai Kensei
Department of Hematology and Oncology, Nagoya Daini Red Cross Hospital, Aichi, Japan; Department of Hematology, Tokai Central Hospital, Higashijimacho, Sohara, Kakamigahara, Gifu, Japan.
Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan.
Lancet Haematol. 2016 Mar;3(3):e107-18. doi: 10.1016/S2352-3026(15)00284-7. Epub 2016 Feb 12.
Patients with adult T-cell leukaemia-lymphoma have few treatment options after relapse and poor survival outcomes with current therapies. We aimed to determine the maximum tolerated dose of lenalidomide, an oral immunomodulator, in Japanese patients with relapsed adult T-cell leukaemia-lymphoma and other peripheral T-cell lymphomas.
In this phase 1 study, we enrolled patients aged 20 years or older with Eastern Cooperative Oncology Group performance status 0-2, documented diagnosis of aggressive adult T-cell leukaemia-lymphoma or other peripheral T-cell lymphoma subtypes, and at least one previous antilymphoma therapy. Patients were sequentially assigned to lenalidomide 25 mg/day, days 1-21 of a 28-day cycle (cohort 1), 25 mg/day continuously (cohort 2), and 35 mg/day continuously (cohort 3) in a 3 + 3 design. The primary study endpoint was to identify the maximum tolerated dose of lenalidomide. Analyses were performed per protocol for efficacy and in the intent-to-treat patient population for safety. This completed trial is registered with ClinicalTrials.gov, number NCT01169298.
We enrolled 14 patients from six centres in Japan. Of 13 assessable patients (nine with adult T-cell leukaemia-lymphoma, four with other peripheral T-cell lymphomas) receiving lenalidomide, dose-limiting toxic effects were reported in three patients during cycle 1 (one grade 4 thrombocytopenia [cohort 2], one grade 3 QT prolongation on electrocardiogram [cohort 3], and one grade 3 fatigue and grade 4 thrombocytopenia [cohort 3]). The maximum tolerated dose was identified as lenalidomide 25 mg/day given continuously. The most common grade 3 or worse adverse events were neutropenia (eight [62%] patients), lymphopenia (seven [54%] patients), and thrombocytopenia (four [31%] patients); myelosuppression was similar in each cohort. Serious adverse events occurred in eight (62%) patients; thrombocytopenia, which occurred in three (23%) patients, was the only serious adverse event reported in more than one patient.
We were able to determine the dose and schedule for lenalidomide treatment in previously treated patients with aggressive, adult T-cell leukaemia-lymphoma. This dose will be used in a subsequent phase 2 study.
Celgene Corporation.
成人T细胞白血病-淋巴瘤患者复发后治疗选择有限，当前疗法的生存预后较差。我们旨在确定来那度胺（一种口服免疫调节剂）在日本复发的成人T细胞白血病-淋巴瘤及其他外周T细胞淋巴瘤患者中的最大耐受剂量。
在这项1期研究中，我们纳入了年龄在20岁及以上、东部肿瘤协作组体能状态为0 - 2、确诊为侵袭性成人T细胞白血病-淋巴瘤或其他外周T细胞淋巴瘤亚型且至少接受过一次抗淋巴瘤治疗的患者。采用3 + 3设计，患者依次被分配接受来那度胺25 mg/天，在28天周期的第1 - 21天给药（队列1），持续25 mg/天给药（队列2），以及持续35 mg/天给药（队列3）。主要研究终点是确定来那度胺的最大耐受剂量。按方案进行疗效分析，在意向性治疗患者群体中进行安全性分析。这项完成的试验已在ClinicalTrials.gov注册，编号为NCT01169298。
我们从日本的6个中心招募了14名患者。在13名接受来那度胺治疗的可评估患者中（9名成人T细胞白血病-淋巴瘤患者，4名其他外周T细胞淋巴瘤患者），1名患者在第1周期出现剂量限制性毒性反应（1例4级血小板减少[队列2]，1例心电图显示3级QT延长[队列3]，1例3级疲劳和4级血小板减少[队列3]）。最大耐受剂量确定为持续给予来那度胺25 mg/天。最常见的3级或更严重不良事件为中性粒细胞减少（8例[62%]患者）、淋巴细胞减少（7例[54%]患者）和血小板减少（4例[31%]患者）；各队列中的骨髓抑制情况相似。8例（62%）患者发生严重不良事件；血小板减少发生在3例（23%）患者中，是唯一报告的有不止1例患者发生的严重不良事件。
我们能够确定来那度胺在既往接受过治疗的侵袭性成人T细胞白血病-淋巴瘤患者中的治疗剂量和给药方案。该剂量将用于后续的2期研究。
新基公司。
