Division of Hematology/Oncology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE, USA.
Department of Lymphoma/Multiple Myeloma, MD Anderson Cancer Center, Houston, TX, USA.
Ann Hematol. 2022 Feb;101(2):335-340. doi: 10.1007/s00277-021-04692-9. Epub 2021 Oct 20.
Peripheral T-cell lymphomas (PTCL) are a unique subset of lymphomas with a poor prognosis due to limited treatment options. We performed a phase 1 study of carfilzomib in patients with relapsed/refractory PTCL to determine the safety profile and the maximum tolerated dose (MTD) of this agent. The study was a classical 3 + 3 phase 1 design with intra-patient dose escalation allowed beginning on day 8 of cycle 1 and subsequently. Dose-limiting toxicity (DLT) was defined as the occurrence of any grade 3/4 adverse event. Carfilzomib was given on days 1, 2, 8, 9, 15, and 16 of a 28-day cycle. Fifteen patients were enrolled from 3 centers. The median age of patients was 62. The median number of prior therapies for subjects on this trial was five. The MTD of carfilzomib was 36 mg/m. Dose-limiting toxicities included anemia and sepsis. Serious adverse events were seen in 45% of patients. Single-agent carfilzomib leads to a complete response in one patient and a partial response in one patient. Overall, the drug was reasonably tolerated for a heavily pretreated population, but the limited response rate and short duration of response demonstrate a lack of promise for carfilzomib as a single agent in this patient population.
外周 T 细胞淋巴瘤（PTCL）是一组具有独特特征的淋巴瘤，由于治疗选择有限，预后较差。我们进行了一项卡非佐米治疗复发/难治性 PTCL 患者的 1 期研究，以确定该药物的安全性特征和最大耐受剂量（MTD）。该研究采用经典的 3+3 1 期设计，允许在第 1 周期的第 8 天开始进行患者内剂量递增，随后进行剂量递增。剂量限制性毒性（DLT）定义为任何 3/4 级不良事件的发生。卡非佐米在 28 天周期的第 1、2、8、9、15 和 16 天给药。该试验从 3 个中心共招募了 15 名患者。患者的中位年龄为 62 岁。本试验中患者之前接受的治疗中位数为 5 种。卡非佐米的 MTD 为 36mg/m。DLT 包括贫血和败血症。45%的患者出现严重不良事件。单药卡非佐米使 1 例患者获得完全缓解，1 例患者获得部分缓解。总的来说，对于预处理较多的患者，该药物具有合理的耐受性，但有限的反应率和较短的反应持续时间表明，卡非佐米作为该患者人群的单一药物没有太大的前景。
