Hess Georg, Wagner Karola, Keller Ulrich, La Rosee Paul, Atta Johannes, Hübel Kai, Lerchenmueller Christian, Schoendube Daniel, Witzens-Harig Mathias, Ruckes Christian, Medler Christoph, van Oordt Christina, Klapper Wolfram, Theobald Matthias, Dreyling Martin
Department of Internal Medicine III (Hematology, Oncology, Pneumology), University Medical Center of the Johannes Gutenberg-University, Mainz, Germany.
Department of Hematology, Oncology, Charité - University Medical School Berlin, Berlin Germany.
Hemasphere. 2020 Jun 8;4(3):e398. doi: 10.1097/HS9.0000000000000398. eCollection 2020 Jun.
In this phase I/II study, we explored the combination of Temsirolimus with Bendamustine and Rituximab (BeRT) in patients with relapsed or refractory (r/r) follicular lymphoma (FL) or mantle cell lymphoma (MCL). Patients with 1 to 3 previous therapies received Bendamustine (90 mg/m, day 1 + 2) and Rituximab (375 mg/m, day 1) with Temsirolimus in doses from 25 to 75 mg in phase I and 50 mg Temsirolimus in phase II, added on day 1, 8, 15 of a 28 days cycle. The primary endpoint of the phase II was ORR at the end of treatment. Overall, 39 (29 MCL, 10 FL) patients were included. Median age was 71 years and median pretreatment number was 2. Grade 3/4 non-hematologic adverse events were rare and included hyperglycemia in 3 patients (7%) and angioedema in 2 patients (5%). Infectious complications grade 3/4 were observed in 9 patients (23%). Hematologic grade 3/4 events included leukopenia in 22 (56%), neutropenia in 18 (46%), lymphopenia in 16 (41%) and thrombocytopenia in 14 patients (36%). An objective response (best response) was observed in 33/39 patients (89%; 24 MCL (89%) and 9 FL (90%)), including 14 CR (38%; 12 MCL (36%) and 2 FL (20%)). Median PFS is 1.5y for MCL and 1.82 years for FL, and median OS has not been reached for either entity. This data demonstrates promising efficacy of Temsirolimus in r/r MCL and FL with acceptable toxicity. The BeRT regimen may be used as a treatment option for both entities.
在这项I/II期研究中，我们探究了替西罗莫司与苯达莫司汀和利妥昔单抗（BeRT）联合用于复发或难治性（r/r）滤泡性淋巴瘤（FL）或套细胞淋巴瘤（MCL）患者的疗效。接受过1至3次既往治疗的患者接受苯达莫司汀（90mg/m²，第1天和第2天）和利妥昔单抗（375mg/m²，第1天）治疗，在I期研究中联合使用剂量为25至75mg的替西罗莫司，在II期研究中联合使用50mg替西罗莫司，于28天周期的第1天、第8天和第15天添加。II期研究的主要终点为治疗结束时的客观缓解率（ORR）。总体而言，共纳入39例患者（29例MCL，10例FL）。中位年龄为71岁，中位预处理次数为2次。3/4级非血液学不良事件罕见，包括3例患者（7%）出现高血糖和2例患者（5%）出现血管性水肿。9例患者（23%）观察到3/4级感染并发症。血液学3/4级事件包括22例患者（56%）出现白细胞减少、18例患者（46%）出现中性粒细胞减少、16例患者（41%）出现淋巴细胞减少以及14例患者（36%）出现血小板减少。33/39例患者（89%；24例MCL（89%）和9例FL（90%））观察到客观缓解（最佳缓解），包括14例完全缓解（CR，38%；12例MCL（36%）和2例FL（20%））。MCL的中位无进展生存期（PFS）为1.5年，FL为1.82年，两种疾病的中位总生存期（OS）均未达到。该数据表明替西罗莫司在r/r MCL和FL中具有良好疗效且毒性可接受。BeRT方案可作为这两种疾病的一种治疗选择。
