Rituximab using a thrice weekly dosing schedule in B-Cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity
Rituximab using a thrice weekly dosing schedule in B-Cell chronic lymphocytic leukemia and small lymphocytic lymphoma demonstrates clinical activity and acceptable toxicity
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DOI：
10.1200/jco.2001.19.8.2153
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发表时间：
2001-04-15
影响因子：
45.3
通讯作者：
Flinn, IW
中科院分区：
文献类型：
--
作者：
Byrd, JC;Murphy, T;Flinn, IW
目的：据报道，利妥昔单抗在小淋巴细胞淋巴瘤（SLL）/慢性淋巴细胞白血病（CLL）中几乎没有活性，并且与显著的输注相关毒性相关。本研究旨在减少初始毒性和优化pharmocotenetics与替代treatment schedule.Patients和方法：33例SLL/CLL患者接受了利妥昔单抗（100毫克）超过4小时的剂量1。在队列I（n = 3; 250 mg/m2）和队列II（n = 7; 375 mg/m2）中，利妥昔单抗在第3天给药，此后使用标准给药方案每周给药3次，持续4周。队列III（n = 23; 375 mg/m2）给予利妥昔单抗类似于队列II的前两个treatments，然后超过1 hour after.Results：共33 CLL/SLL患者参加，只有一个病人因为输注相关的毒性而停止治疗。与未发生此类反应的患者相比，13例患者发生一过性低氧血症、低血压或呼吸困难，与基线白细胞介素-6、白细胞介素-8、肿瘤坏死因子α和干扰素γ的显著变化相关。输注相关毒性更常见于年龄较大（中位年龄73 vs 62岁; P = 0.02）且无其他治疗前临床或实验室特征可预测这些事件发生的患者。总缓解率为45%（3% CR，42% PR; 95% CI 28%-64%）。这15例患者的中位反应持续时间为10个月（95%CI，6.8-13.2;范围，3至17+）。结论：每周三次给予利妥昔单抗4周显示临床疗效和可接受的毒性。初始输注相关事件似乎是细胞因子介导的，并通过第三次输注解决，从而使快速给药成为可能。利妥昔单抗与其他治疗CLL的未来联合研究似乎是必要的。(C)2001年，美国临床肿瘤学会。
Purpose: Rituximab has been reported to have little activity in small lymphocytic lymphoma (SLL)/chronic lymphocytic leukemia (CLL) and to be associated with significant infusion-related toxicity. This study sought to decrease the initial toxicity and optimize the pharmocokinetics with an alternative treatment schedule.Patients and Methods: Thirty three patients with SLL/CLL received dose 1 of rituximab (100 mg) over 4 hours. In cohort I (n = 3; 250 mg/m(2)) and cohort II (n = 7; 375 mg/m2) rituximab was administered on day 3 and thereafter three times weekly for 4 weeks using a standard administration schedule. Cohort Ill(n = 23; 375 mg/m2) administered rituximab similar to cohort II for the first two treatments and then over 1 hour thereafter.Results: A total of 33 CLL/SLL patients were enrolled; only one patient discontinued therapy because of infusion-related toxicity. Thirteen patients developed transient hypoxemia, hypotension, or dyspnea that were associated with significant changes in baseline interleukin-6, interleukin-8, tumor necrosis factor alpha, and interferon gamma compared with those not experiencing such reactions. Infusion-related toxicity occurred more commonly in older (median age 73 v 62 years; P = .02) patients with no other pretreatment clinical or laboratory Features predicting occurrence of these events. The overall response rate was 45% (3% CR, 42% PR; 95% CI 28% to 64%). Median response duration for these 15 patients was 10 months (95% CI, 6.8-13.2; range, 3 to 17+).Conclusion: Rituximab administered thrice weekly for 4 weeks demonstrates clinical efficacy and acceptable toxicity. Initial infusion-related events seem to be cytokine mediated and resolve by the third infusion making rapid administration possible. Future combination studies of rituximab with other therapies in CLL seem warranted. (C) 2001 by American Society of Clinical Oncology.