钇-90标记的替伊莫单抗放射免疫疗法与利妥昔单抗免疫疗法治疗复发或难治性低度、滤泡性或转化型B细胞非霍奇金淋巴瘤患者的随机对照试验

Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin's lymphoma.

作者信息

Witzig Thomas E, Gordon Leo I, Cabanillas Fernando, Czuczman Myron S, Emmanouilides Christos, Joyce Robin, Pohlman Brad L, Bartlett Nancy L, Wiseman Gregory A, Padre Norman, Grillo-López Antonio J, Multani Pratik, White Christine A

机构信息

Division of Internal Medicine and Hematology, Nuclear Medicine, Mayo Clinic and Mayo Foundation, 60 Stabile Building, Rochester, MN 55905, USA.

出版信息

J Clin Oncol. 2002 May 15;20(10):2453-63. doi: 10.1200/JCO.2002.11.076.

DOI:10.1200/JCO.2002.11.076

PMID:12011122

Abstract

PURPOSE

Radioimmunotherapy combines biologic and radiolytic mechanisms to target and destroy tumor cells, thus offering a needed therapeutic alternative for refractory non-Hodgkin's lymphoma (NHL) patients. This phase III randomized study compares the novel radioimmunotherapy yttrium-90 ((90)Y) ibritumomab tiuxetan with a control immunotherapy, rituximab, in 143 patients with relapsed or refractory low-grade, follicular, or transformed CD20(+) transformed NHL.

PATIENTS AND METHODS

Patients received either a single intravenous (IV) dose of (90)Y ibritumomab tiuxetan 0.4 mCi/kg (n = 73) or rituximab 375 mg/m(2) IV weekly for four doses (n = 70). The radioimmunotherapy group was pretreated with two rituximab doses (250 mg/m(2)) to improve biodistribution and one dose of indium-111 ibritumomab tiuxetan for imaging and dosimetry. The primary end point, overall response rate (ORR), was assessed by an independent, blinded, lymphoma expert panel.

RESULTS

ORR was 80% for the (90)Y ibritumomab tiuxetan group versus 56% for the rituximab group (P =.002). Complete response (CR) rates were 30% and 16% in the (90)Y ibritumomab tiuxetan and rituximab groups, respectively (P =.04). An additional 4% achieved an unconfirmed CR in each group. Kaplan-Meier estimated median duration of response was 14.2 months in the (90)Y ibritumomab tiuxetan group versus 12.1 months in the control group (P =.6), and time to progression was 11.2 versus 10.1 months (P =.173) in all patients. Durable responses of > or = 6 months were 64% versus 47% (P =.030). Reversible myelosuppression was the primary toxicity noted with (90)Y ibritumomab tiuxetan.

CONCLUSION

Radioimmunotherapy with (90)Y ibritumomab tiuxetan is well tolerated and produces statistically and clinically significant higher ORR and CR compared with rituximab alone.

摘要

目的

放射免疫疗法结合生物学和放射分解机制来靶向并破坏肿瘤细胞，从而为难治性非霍奇金淋巴瘤（NHL）患者提供了一种必要的治疗选择。这项III期随机研究在143例复发或难治性低度、滤泡性或转化型CD20(+)转化型NHL患者中，将新型放射免疫疗法钇-90（90Y）替伊莫单抗与对照免疫疗法利妥昔单抗进行了比较。

患者与方法

患者接受单次静脉注射（IV）剂量的90Y替伊莫单抗0.4 mCi/kg（n = 73）或利妥昔单抗375 mg/m²静脉注射，每周一次，共四次（n = 70）。放射免疫疗法组预先接受两剂利妥昔单抗（250 mg/m²）以改善生物分布，并接受一剂铟-111替伊莫单抗用于成像和剂量测定。主要终点，即总缓解率（ORR），由一个独立、盲法的淋巴瘤专家小组进行评估。

结果

90Y替伊莫单抗组的ORR为80%，而利妥昔单抗组为56%（P = 0.002）。90Y替伊莫单抗组和利妥昔单抗组的完全缓解（CR）率分别为30%和16%（P = 0.04）。每组另外有4%达到未经确认的CR。Kaplan-Meier估计90Y替伊莫单抗组的中位缓解持续时间为14.2个月，而对照组为12.1个月（P = 0.6），所有患者的疾病进展时间分别为11.2个月和10.1个月（P = 0.173）。持续缓解≥6个月的比例分别为64%和47%（P = 0.030）。可逆性骨髓抑制是90Y替伊莫单抗观察到的主要毒性。