Frankel Arthur E, Woo Jung H, Ahn Chul, Pemmaraju Naveen, Medeiros Bruno C, Carraway Hetty E, Frankfurt Olga, Forman Stephen J, Yang Xuezhong A, Konopleva Marina, Garnache-Ottou Francine, Angelot-Delettre Fanny, Brooks Christopher, Szarek Michael, Rowinsky Eric
University of Texas Southwestern Medical Center, Dallas, TX;
Baylor Scott & White Health, Temple, TX;
Blood. 2014 Jul 17;124(3):385-92. doi: 10.1182/blood-2014-04-566737. Epub 2014 May 23.
This is the first prospective study of treatment of patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN), an aggressive hematologic malignancy derived from plasmacytoid dendritic cells that typically involves the skin and rapidly progresses to a leukemia phase. Despite being initially responsive to intensive combination chemotherapy, most patients relapse and succumb to their disease. Because BPDCN blasts overexpress the interleukin-3 receptor (IL3R), the activity of SL-401, diptheria toxin (DT)388IL3 composed of the catalytic and translocation domains of DT fused to IL3, was evaluated in BPDCN patients in a phase 1-2 study. Eleven patients were treated with a single course of SL-401 at 12.5 μg/kg intravenously over 15 minutes daily for up to 5 doses; 3 patients who had initial responses to SL-401 received a second course in relapse. The most common adverse events including fever, chills, hypotension, edema, hypoalbuminemia, thrombocytopenia, and transaminasemia were transient. Seven of 9 evaluable (78%) BPDCN patients had major responses including 5 complete responses and 2 partial responses after a single course of SL-401. The median duration of responses was 5 months (range, 1-20+ months). Further studies of SL-401 in BPDCN including those involving multiple sequential courses, alternate schedules, and combinations with other therapeutics are warranted. This trial is registered at clinicaltrials.gov as #NCT00397579.
这是一项关于治疗母细胞性浆细胞样树突状细胞肿瘤（BPDCN）患者的前瞻性研究。BPDCN是一种侵袭性血液系统恶性肿瘤，起源于浆细胞样树突状细胞，通常累及皮肤，并迅速进展至白血病阶段。尽管最初对强化联合化疗有反应，但大多数患者会复发并死于该疾病。由于BPDCN原始细胞过度表达白细胞介素-3受体（IL3R），因此在一项1-2期研究中，对BPDCN患者评估了SL-401（由与IL3融合的DT催化和转位结构域组成的白喉毒素（DT）388IL3）的活性。11例患者接受了单疗程的SL-401治疗，剂量为12.5μg/kg，静脉滴注15分钟，每日1次，最多5剂；3例对SL-401有初始反应的患者在复发时接受了第二疗程治疗。最常见的不良事件包括发热、寒战、低血压、水肿、低白蛋白血症、血小板减少和转氨酶血症，均为短暂性。9例可评估的BPDCN患者中有7例（78%）出现主要反应，其中单疗程SL-401治疗后5例完全缓解，2例部分缓解。反应的中位持续时间为5个月（范围1-20+个月）。有必要对BPDCN患者进一步开展关于SL-401的研究，包括涉及多个连续疗程、交替给药方案以及与其他治疗方法联合使用的研究。该试验已在clinicaltrials.gov上注册，编号为#NCT00397579。
