Department of Hematology, Yamagata University Hospital, Yamagata, Japan.
Department of Hematology Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
Cancer Chemother Pharmacol. 2022 Jul;90(1):83-95. doi: 10.1007/s00280-022-04442-2. Epub 2022 Jul 7.
This phase I/II clinical study was conducted to examine the safety, tolerability, pharmacokinetics, and efficacy of 10-min dosing of bendamustine in patients with previously untreated indolent B-cell non-Hodgkin lymphoma (iNHL) or mantle cell lymphoma (MCL) (Group 1) and patients with relapsed/refractory diffuse large B-cell lymphoma (rrDLBCL) (Group 2).
Rituximab 375 mg/m was administered intravenously every 28 days to Group 1 patients on day 1 and every 21 days to Group 2 patients on day 1. Bendamustine 90 mg/m/day was administered to the former on days 1 and 2; bendamustine 120 mg/m/day was administered to the latter on days 2 and 3. Each regimen was delivered up to six cycles for both groups. The primary endpoints were safety and tolerability in Groups 1 and 2, respectively.
Among 37 enrolled patients, safety was assessed in 36. In Group 1 (n = 30), 27 patients (90%) had follicular lymphoma. Adverse events (AEs) were observed in all 30 patients in Group 1. Dose-limiting toxicities were observed in two of six patients in Group 2. Common AEs included lymphocyte count decreased (86.7%, 100%). In Group 1, overall response and complete response rates were 93.1% (95% confidence interval [CI] 77.2-99.2%) and 75.9% (95% CI 56.5-89.7%), respectively. The C and AUC of bendamustine tended to be higher in Group 2 than in Group 1.
This study showed that bendamustine is safe, well-tolerated and effective for patients with previously untreated iNHL, MCL or rrDLBCL. Pharmacokinetic data were equivalent to those obtained outside of Japan.
Registration NCT03900377; registered April 3, 2019.
本 I/II 期临床试验旨在研究未经治疗的惰性 B 细胞非霍奇金淋巴瘤（iNHL）或套细胞淋巴瘤（MCL）患者（第 1 组）和复发/难治性弥漫性大 B 细胞淋巴瘤（rrDLBCL）患者（第 2 组）接受 10 分钟苯达莫司汀给药的安全性、耐受性、药代动力学和疗效。
第 1 组患者在第 1 天和第 28 天接受静脉注射利妥昔单抗 375mg/m2，第 2 组患者在第 1 天和第 21 天接受静脉注射利妥昔单抗 375mg/m2。第 1 组患者在第 1 天和第 2 天接受苯达莫司汀 90mg/m2/天；第 2 组患者在第 2 天和第 3 天接受苯达莫司汀 120mg/m2/天。两组均每 6 个周期给药。第 1 组和第 2 组的主要终点分别为安全性和耐受性。
在 37 名入组患者中，36 名患者接受了安全性评估。第 1 组（n=30）中 27 名患者（90%）患有滤泡性淋巴瘤。第 1 组 30 名患者均出现不良反应（AE）。第 2 组 6 名患者中有 2 名出现剂量限制性毒性。常见的 AE 包括淋巴细胞计数减少（86.7%，100%）。第 1 组患者的总缓解率和完全缓解率分别为 93.1%（95%置信区间[CI]77.2-99.2%）和 75.9%（95% CI 56.5-89.7%）。第 2 组患者的苯达莫司汀 C 和 AUC 均高于第 1 组。
该研究表明，苯达莫司汀治疗未经治疗的 iNHL、MCL 或 rrDLBCL 患者安全、耐受且有效。药代动力学数据与日本以外的研究结果相当。
NCT03900377；于 2019 年 4 月 3 日注册。
