Frankel Arthur E, Surendranathan Asha, Black Jennifer H, White Angela, Ganjoo Kristen, Cripe Larry D
Department of Medicine, Scott and White Hospital, Temple, Texas 76508, USA.
Cancer. 2006 May 15;106(10):2158-64. doi: 10.1002/cncr.21851.
The safety and efficacy of the interleukin-2 diphtheria toxin fusion protein (DAB(389)IL2; denileukin diftitox) directed against the IL-2 receptor (IL-2R) was tested in patients with recurrent or refractory chronic lymphocytic leukemia (CLL).
Denileukin diftitox was administered as 60-minute intravenous infusions for 5 days every 21 days at a dose of 18 mug/kg per day for up to 8 cycles. In total, 28 patients were treated in 2 multiinstitutional studies with similar eligibility criteria and treatment protocols. Twenty-two patients receive > or = 2 cycles of denileukin diftitox and were evaluable for response.
Twelve of 22 patients achieved reductions of peripheral CLL cells, with 5 of 12 patients achieving >80% reductions. Six of 22 patients achieved reductions in the size of lymph node on examination and computed tomography scans, and all 6 of those patients met the criteria for a partial or complete response that lasted > or = 2 months. Bone marrow biopsies before and after treatment confirmed a complete remission that lasted for 1 year in 1 patient. Overall, denileukin diftitox produced complete remission in 1 of 22 patients (4%) and partial remission in 5 of 22 patients (23%) for a total remission rate of 27%. Progression-free intervals in the responders were 2 months in 2 patients and 4 months, 6 months, 7 months, and 12 months in 1 patient each. Toxicities were moderate. No infections associated with immunosuppression were seen. There was no significant correlation of response or toxicities with the numbers of denileukin diftitox cycles received or with CD25 levels.
Follow-up studies will be required to identify predictors of response that may improve the response rate to denileukin diftitox in patients with CLL.
针对白细胞介素-2受体（IL-2R）的白细胞介素-2 白喉毒素融合蛋白（DAB(389)IL2；地尼白介素）的安全性和有效性在复发或难治性慢性淋巴细胞白血病（CLL）患者中进行了测试。
地尼白介素每21天静脉输注60分钟，持续5天，剂量为每天18μg/kg，最多8个周期。在两项具有相似入选标准和治疗方案的多机构研究中，共治疗了28例患者。22例患者接受了≥2个周期的地尼白介素治疗，并可评估疗效。
22例患者中有12例外周血CLL细胞减少，其中12例中有5例减少>80%。22例患者中有6例经体格检查和计算机断层扫描显示淋巴结大小减小，所有6例患者均符合持续≥2个月的部分或完全缓解标准。1例患者治疗前后的骨髓活检证实完全缓解持续了1年。总体而言，地尼白介素在22例患者中产生了1例完全缓解（4%）和5例部分缓解（23%），总缓解率为27%。缓解者的无进展生存期在2例患者中为2个月，在1例患者中分别为4个月、6个月、7个月和12个月。毒性为中度。未观察到与免疫抑制相关的感染。缓解或毒性与接受的地尼白介素周期数或CD25水平之间无显著相关性。
需要进行后续研究以确定可能提高CLL患者对地尼白介素反应率的反应预测因素。
