Randomized phase II study of interleukin-12 in combination with rituximab in previously treated non-Hodgkin's lymphoma patients
Randomized phase II study of interleukin-12 in combination with rituximab in previously treated non-Hodgkin's lymphoma patients
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DOI：
10.1158/1078-0432.ccr-06-1245
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发表时间：
2006-10-15
影响因子：
11.5
通讯作者：
Witzig, Thomas E.
中科院分区：
文献类型：
--
作者：
Ansell, Stephen M.;Geyer, Susan M.;Witzig, Thomas E.
目的：利妥昔单抗是一种能诱导B细胞凋亡并募集免疫效应细胞介导细胞溶解的嵌合抗体。白细胞介素-12（IL-12）促进T细胞和自然杀伤细胞的细胞溶解反应。该II期研究是为了确定IL-12与利妥昔单抗联合治疗B细胞非霍奇金淋巴瘤（NHL）患者的疗效和毒性。58例经组织学证实的复发性B细胞NHL患者随机接受利妥昔单抗和IL-12联合治疗（A组）或利妥昔单抗联合IL-12治疗（B组）。12例在利妥昔单抗治疗后记录无应答或进展后（B组）。治疗包括在第1、8、15和22天给予375 mg/m2利妥昔单抗和300 ng/kg IL-12 s.c. A组从第2天开始每周两次，或B组在进展时每周两次。结果：A组的总应答率为37%（30例中的11例），B组为52%（25例中的13例）。在B组中观察到的所有反应都发生在患者接受利妥昔单抗时，并且在随后的IL-12治疗期间没有反应发生。A组的中位缓解持续时间为16个月，B组为12个月。活检标本连续获得的一个子集的患者，并表明，基因表达的变化是不同的，从外周血细胞相比，从淋巴结biopsizes.Conclusions细胞：IL-12和利妥昔单抗的伴随使用有适度的疾病活动在B细胞NHL患者，但IL-12利妥昔单抗后的顺序管理并没有导致额外的临床反应。
Purpose: Rituximab is a chimeric antibody that induces B-cell apoptosis and recruits immune effector cells to mediate cell lysis. Interleukin-12 (IL-12) facilitates cytolytic responses by T cells and natural killer cells. This phase II study was done to determine the efficacy and toxicity of IL-12 in combination with rituximab in patients with B-cell non-Hodgkin's lymphoma (NHL).Experimental Design: Fifty-eight patients with histologically confirmed relapsed B-cell NHL were randomized to receive concurrent treatment with rituximab and IL-12 (arm A) or rituximab with subsequent treatment with IL-12 after documented nonresponse or progression after rituximab (arm B). Treatment consisted of 375 mg/m(2) rituximab on days 1, 8, 15, and 22 and 300 ng/kg IL-12 given s.c. twice weekly starting on day 2 for arm A or upon progression for arm B.Results:The overall response rate was 37% (11 of 30) in arm A and 52% (13 of 25) in arm B. All of the responses seen in arm B occurred while patients received rituximab, and no responses occurred during treatment with subsequent IL-12. The median duration of response was 16 months for arm A and 12 months for arm B. Biopsy specimens were serially obtained in a subset of patients and showed that changes in gene expression were different when cells from the peripheral blood were compared with cells from lymph node biopsies.Conclusions: The concomitant use of IL-12 and rituximab had modest disease activity in patients with B-cell NHL, but the sequential administration of IL-12 after rituximab did not result in additional clinical responses.