Phase 1/2 study of fractionated 131I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy
Phase 1/2 study of fractionated 131I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy
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DOI：
10.1182/blood-2008-08-175653
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发表时间：
2009-02-12
期刊：
影响因子：
20.3
通讯作者：
Johnson, Peter W. M.
中科院分区：
文献类型：
--
作者：
Illidge, Tim M.;Bayne, Mike;Johnson, Peter W. M.
多剂量利妥昔单抗诱导治疗对抗CD20放射免疫治疗后续疗效和毒性的影响尚不清楚。我们评估了一种新的方案，在复发的惰性B细胞淋巴瘤中，每周4次静脉滴注375 mg/m(2)利妥昔单抗，然后是2次I-131-利妥昔单抗，然后是100 mg/m(2)预剂量的利妥昔单抗。利妥昔单抗诱导治疗显著延长了I-131-利妥昔单抗的有效半衰期(P=.003)，诱导治疗后高水平的利妥昔单抗与放射免疫结合物的有效半衰期延长有关(P=.009)。肿瘤负荷较大的患者在第一组分和第二组分之间I-131-利妥昔单抗的有效半衰期显著增加(P=0.007)。多剂量利妥昔单抗诱导治疗似乎不会影响随后的I-131-利妥昔单抗放射免疫治疗的临床疗效或增加毒性。总有效率为94%，完全有效率为50%。中位进展时间为20个月，显著长于最后一次合格化疗(P=.001)。I-131-利妥昔单抗的分级允许全身累积剂量超过120cGY，比以前单次注射小鼠放射免疫结合物获得的剂量高约60%，而没有明显的血液毒性。(血。2009年；113：1412-1421)
The effect of induction therapy with multiple doses of rituximab on the subsequent efficacy and toxicity of anti-CD20 radioimmunotherapy is unknown. We evaluated a novel protocol using 4 weekly infusions of 375 mg/m(2) rituximab followed by 2 fractions of I-131-rituximab, preceded by a 100-mg/m(2) predose of rituximab, in relapsed indolent B-cell lymphoma. Induction therapy with rituximab significantly increased the effective half-life of I-131-rituximab (P = .003) and high serum levels of rituximab after induction therapy correlated with increased effective half-life of the radioimmunoconjugate (P = .009). Patients with large tumor burdens experienced significant increases in the effective half-life of I-131-rituximab between delivery of the first and second fractions (P = .007). Induction therapy with multiple doses of rituximab did not appear to compromise the clinical efficacy or increase toxicity of subsequent I-131-rituximab radioimmunotherapy. The overall response rate was 94%, with complete response rate 50%. The median time to progression was 20 months, significantly longer than for the last qualifying chemotherapy (P = .001). Fractionation of I-131-rituximab allowed cumulative whole-body doses of more than 120 cGy, approximately 60% greater than those previously achieved with a single administration of a murine radioimmunconjugate, to be delivered without significant hematologic toxicity. (Blood. 2009; 113: 1412-1421)