医脉通编译，转载请务必注明出处

2016年6月3-7日，一年一度的美国临床肿瘤学会（American Society of Clinical Oncology，ASCO）年会将在芝加哥举办。6月4，下午3：00到6：00血液肿瘤口头报告专场上，一项摘要号为7006的多中心2期试验探讨了SL-401治疗母细胞性浆细胞样树突状细胞肿瘤（BPDCN）的疗效，医脉通整理如下：

‍

SL-401是一种靶向白介素-3受体（CD123）药物。CD123在BPDCN和其它血液肿瘤中过表达。BPDCN是一种罕见类型高度侵袭性血液肿瘤，除侵犯皮肤外还侵犯骨髓和淋巴结。本文报道了多中心2期试验结果。

【方法】

该项2期试验包括导入（1阶段）和扩张（2阶段）两个阶段。第1阶段，BPDCN和复发/难治性（r/r）AML患者接受剂量为7、9、12或16 ug/kg的 SL-401常规IV输注，持续达5个剂量，每21天重复治疗。第2阶段，患者接受SL-401第1阶段最佳剂量治疗。

【结果】

自1/20/16起，18名BPDCN患者（1&2阶段：9+9；包括未被评估的2名患者）接受了SL-401（7 ug/kg，n=3 [第1阶段]；12 ug/kg，n=15 [1&2阶段：6+9]），中位年龄为70岁；30名r/r AML患者（1&2阶段：14+16）被分开报道。

第1阶段，12 ug/kg是第2阶段中BPDCN患者的最大检测/推荐剂量，是r/r AML患者的最大耐受量（MTD）；BPDCN患者的MTD未达到。最常见的所有级别的治疗相关不不良反应（AEs）是暂时性转氨酶升高（57%）和低蛋白血症（40%）。试验中也发生了短暂性血小板减少症（15%）。2名1阶段患者发生了毛细血管漏综合征（CLS）：gr 5 （7 ug/kg）和gr 4 （12 ug/kg）。研究人员给予患者安全事件控制策略，成功地将严重CLS风险最小化（剂量达12 ug/kg，仍未出现严重CLS））。可评估BPDCN患者ORR为87% （13/15），并且皮肤、古寺、淋巴结及内脏相关病变率明显下降。一线治疗和r/r AML治疗的ORR分别为100% （10/10）和60% （3/5）。所有接受剂量为12 ug/kg作为一线治疗的8名患者达到了CR （n=5）或临床CR （CRc）（n=3），其中6名患者在缓解期继续接受了SL-401治疗（n=4；持续期数据在3 +~8 +疗程）或顺利转至干细胞移植（n=2；第7，4疗程后，1 CR，1 CRc）。

【结论】

SL-401单药治疗BPDCN的疗效很好，包括一线治疗100%的ORR和所有治疗87%的ORR，并且也达到了多重CRs；响应持续时间日趋成熟并令人鼓舞。

摘要原文:

Results from phase 2 registration trial of SL-401 in patients with blastic plasmacytoid dendritic cell neoplasm (BPDCN): Lead-in completed, expansion stage ongoing. Abstract No:7006

Background: SL-401 is a targeted therapy directed to the interleukin-3 receptor (CD123), a target overexpressed on BPDCN and other hematologic cancers. BPDCN is a rare, aggressive hematologic malignancy of unmet medical need. Results from multicenter Phase 2 completed lead-in and ongoing expansion stage are reported.

Methods: This Phase 2 trial includes a lead-in (stage 1) and expansion (stage 2). In stage 1, BPDCN and relapsed/refractory (r/r) AML pts received SL-401 as a daily IV infusion at 7, 9, 12, or 16 ug/kg for up to 5 doses repeated every 21 days. In stage 2, pts received SL-401 at the optimal stage 1 dose.

Results: As of 1/20/16, 18 BPDCN pts (9+9 in stages 1&2; including 2 pts not yet evaluable) received SL-401 (7 ug/kg, n=3 [stage 1]; 12 ug/kg, n=15 [6+9 in stages 1&2]), median 70 yrs (45-82, and 15 yr compassionate use pt); 30 r/r AML pts (14+16 in stages 1&2) to be reported separately. In stage 1, 12 ug/kg was the maximum tested/recommended stage 2 dose for BPDCN and MTD in r/r AML; MTD was not reached in BPDCN. Most common treatment-related AEs, all grades, are transient transaminase elevation (57%) and hypoalbuminemia (40%). Transient thrombocytopenia was also noted (15%). Two stage 1 pts had capillary leak syndrome (CLS): gr 5 (7 ug/kg) and gr 4 (12 ug/kg). Safety precautions were successfully implemented to minimize risk of severe CLS which has not occurred at doses up to 12 ug/kg since adoption. 87% (13/15) ORR was seen in evaluable BPDCN pts, with marked disease reductions in skin, bone marrow, lymph node, and viscera. ORR was 100% (10/10) in first-line and 60% (3/5) in r/r settings. All 8 first-line patients treated at 12 ug/kg had CR (n=5) or clinical CR (CRc) (n=3). Six of these 8 pts remain on SL-401 in remission (n=4; duration data ongoing at 3+ to 8+ cycles) or were successfully bridged to stem cell transplant (n=2; 1 CR, 1 CRc after 7, 4 cycles).

Conclusions: SL-401 demonstrated robust single-agent activity in BPDCN, including 100% ORR in first-line, and 87% in all-lines, with multiple CRs; response duration data are maturing and encouraging. This trial (NCT02113982) is designed to support registration in BPDCN and updated data will be presented.

会议专题》》》2016年ASCO年会专题报道