Ujjani Chaitra, Ramzi Pari, Gehan Edmund, Wang Hongkun, Wang Yiru, Cheson Bruce D
Department of Hematology and Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Hospital , Washington, DC , USA.
Leuk Lymphoma. 2015 Apr;56(4):915-20. doi: 10.3109/10428194.2014.933217. Epub 2014 Aug 6.
Despite initial responses > 90% with fludarabine and rituximab-based regimens, patients with chronic lymphocytic leukemia (CLL) invariably relapse and require further treatment. Ofatumumab and bendamustine have each shown efficacy in relapsed/refractory CLL with overall response rates (ORRs) of 58% and 76%, respectively. Given excellent data with bendamustine and rituximab in relapsed/refractory CLL/small lymphocytic lymphoma (SLL), this phase II study evaluated the combination of ofatumumab and bendamustine in previously treated patients. Patients received ofatumumab 300 mg intravenously (IV) day - 7, followed by ofatumumab 1000 mg IV day 1 and bendamustine 70 mg/m(2) days 1 and 2 of each 28-day cycle. Patients received 4-6 cycles depending on number of prior therapies, as long as well-tolerated or until progression. Of 10 patients enrolled, the ORR was 40% and complete response rate was 20%. The median progression-free and overall survivals were 8.1 months and 16.2 months. Three patients developed Richter transformation. The study was closed early due to unexpected adverse events including infusion-related reactions, infection and neurotoxicity.
尽管基于氟达拉滨和利妥昔单抗的方案初始缓解率>90%，但慢性淋巴细胞白血病（CLL）患者总会复发并需要进一步治疗。奥法木单抗和苯达莫司汀在复发/难治性CLL中均显示出疗效，总缓解率（ORR）分别为58%和76%。鉴于苯达莫司汀和利妥昔单抗在复发/难治性CLL/小淋巴细胞淋巴瘤（SLL）中的出色数据，这项II期研究评估了奥法木单抗和苯达莫司汀联合用于既往治疗过的患者。患者在第-7天静脉注射（IV）300mg奥法木单抗，随后在第1天静脉注射1000mg奥法木单抗，并在每个28天周期的第1天和第2天静脉注射70mg/m²苯达莫司汀。根据既往治疗次数，患者接受4-6个周期的治疗，只要耐受性良好或直至病情进展。在入组的10例患者中，ORR为40%，完全缓解率为20%。无进展生存期和总生存期的中位数分别为8.1个月和16.2个月。3例患者发生Richter转化。由于出现包括输液相关反应、感染和神经毒性在内的意外不良事件，该研究提前终止。
