Department of Internal Medicine I, Clinical Division of Oncology, Medical University of Vienna, Vienna, USA.
Haematologica. 2011 Jul;96(7):1008-14. doi: 10.3324/haematol.2011.041392. Epub 2011 Apr 12.
Bortezomib belongs to a new class of anti-cancer agents, the proteasome inhibitors, and has documented activity in multiple myeloma and mantle cell lymphoma. Preclinical studies suggest that bortezomib has synergistic activity with rituximab, which provides a rationale for the exploration of treatment combinations.
The activity and safety of bortezomib in combination with rituximab and dexamethasone were investigated in patients with relapsed or chemotherapy-refractory mantle cell lymphoma. A treatment cycle consisted of bortezomib (1.3 mg/m² on days 1, 4, 8, and 11; six 21-day cycles), rituximab (375 mg/m², day 1) and dexamethasone (40 mg orally, days 1 to 4). Responding patients received four consolidating doses of rituximab. Sixteen patients with progressive mantle cell lymphoma after a median of three prior lines of therapy were enrolled.
The overall response rate was 81.3% (13 patients), with seven patients achieving a complete response (43.8%). Six of these patients were also negative for disease activity by positron emission tomography scanning. The median progression-free survival and overall survival were 12.1 and 38.6 months, respectively. In patients achieving a complete response, the median progression-free survival and overall survival have not yet been reached. Adverse events (greater than grade II) included thrombocytopenia (37.5%), fatigue (18.8%) and peripheral neuropathy (12.5%). Two patients discontinued bortezomib because of grade III neuropathy.
Bortezomib combined with rituximab and dexamethasone has promising activity and manageable toxicity in patients with heavily pretreated mantle cell lymphoma. Achievement of complete response emerged as an important factor for sustained disease control. This trial was registered at www.clinicaltrials.gov as #NCT00261612.
硼替佐米属于新型抗癌药物蛋白酶体抑制剂，在多发性骨髓瘤和套细胞淋巴瘤中具有明确的疗效。临床前研究表明，硼替佐米与利妥昔单抗具有协同作用，这为探索联合治疗提供了理论依据。
本研究旨在评估硼替佐米联合利妥昔单抗和地塞米松治疗复发或化疗耐药套细胞淋巴瘤的疗效和安全性。治疗周期包括硼替佐米（第 1、4、8 和 11 天 1.3mg/m²，6 个 21 天周期）、利妥昔单抗（375mg/m²，第 1 天）和地塞米松（40mg 口服，第 1-4 天）。缓解患者接受 4 个疗程的利妥昔单抗巩固治疗。共纳入 16 例接受中位 3 线以上治疗后进展的套细胞淋巴瘤患者。
总体缓解率为 81.3%（13 例），其中 7 例达到完全缓解（43.8%）。6 例患者经正电子发射断层扫描（PET）检查也无疾病活动。中位无进展生存期和总生存期分别为 12.1 个月和 38.6 个月。达到完全缓解的患者，中位无进展生存期和总生存期尚未达到。不良事件（大于 2 级）包括血小板减少（37.5%）、乏力（18.8%）和周围神经病变（12.5%）。2 例患者因 3 级神经病变停止使用硼替佐米。
硼替佐米联合利妥昔单抗和地塞米松治疗经大量预处理的套细胞淋巴瘤具有良好的疗效和可管理的毒性。达到完全缓解是持续疾病控制的重要因素。本研究在 ClinicalTrials.gov 注册，编号为 #NCT00261612。
