Blood:Parsaclisib,高选择性PI3Kδ抑制剂,可有效治疗复发性或难治性B细胞NHL

2019-04-01 MedSci MedSci原创

中心点:Parsaclisib是一种有效的、高选择性的二代PI3Kδ抑制剂,且不会升高转氨酶。摘要:Parsaclisib (INCB050465),是一种有效的高选择性的二代磷脂酰肌醇3激酶δ (PI3Kδ)抑制剂,Andres Forero-Torres等人开展一I/II期研究,评估parsaclisib单独或联合Janus激酶1抑制剂(itacitinib)或化疗(利妥昔单抗、异环磷酰胺、卡

中心点:

Parsaclisib是一种有效的、高选择性的二代PI3Kδ抑制剂,且不会升高转氨酶。

摘要:

Parsaclisib (INCB050465),是一种有效的高选择性的二代磷脂酰肌醇3激酶δ (PI3Kδ)抑制剂,Andres Forero-Torres等人开展一I/II期研究,评估parsaclisib单独或联合Janus激酶1抑制剂(itacitinib)或化疗(利妥昔单抗、异环磷酰胺、卡铂和依托泊苷)用于复发性/难治性B细胞恶性肿瘤患者的疗效和安全性。

共72位患者接受parsaclisib单药(5-45mg/日)治疗。扩展剂量为20和30mg/日;20mg时开始间歇(1/日,持续9周,然后改为1/周)。未观察到剂量限制性毒性,未到达最大耐受剂量。

最常见的非血液学需紧急治疗的副反应(TEAEs)有腹泻/结肠炎(36%)、恶心(36%)、疲劳(31%)和红疹(31%)。19%的患者发生3/4级中性粒细胞减少。重度TEAEs(>2位患者)有腹泻/结肠炎(9位)、发热(4位)、低血压(3位)和败血症(3位)。停药前谷氨酸转氨酶和丙氨酸转氨酶升高均为1级,除了1例继发于败血症的3级。两位患者出现3次致命性的非parsaclisib相关性的TEAEs(呼吸衰竭、呼吸衰竭和败血症)。在非霍奇金淋巴瘤(NHL)中,滤泡性淋巴瘤、边缘线淋巴瘤、套细胞淋巴瘤和弥漫性大B细胞淋巴瘤单药治疗的客观缓解率分别为71%、78%、67%和30%;93%的缓解发生于第一次评估(~9周)。

总而言之,parsaclisib在复发性或难治性B细胞NHL中显示出抗肿瘤活性,具有改善长期患者预后的潜力。II期研究在复发或难治性B细胞NHL亚型正在进行。

原始出处:

Andres Forero-Torres,et al. Parsaclisib, a potent and highly selective PI3Kδ inhibitor, in patients with relapsed or refractory B-cell malignancies.Blood 2019 :blood-2018-08-867499; doi: https://doi.org/10.1182/blood-2018-08-867499 

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    2020-02-10 mhm289
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    2019-10-24 jklm09
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href='/topic/show?id=b46f12e81ed' target=_blank style='color:#2F92EE;'>#NHL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12781, encryptionId=b46f12e81ed, topicName=NHL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f7839003589, createdName=yzh402, createdTime=Wed Apr 03 03:20:00 CST 2019, time=2019-04-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1333214, encodeId=85bc13332142e, content=<a href='/topic/show?id=ecfa1423117' target=_blank style='color:#2F92EE;'>#PI3K#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14231, encryptionId=ecfa1423117, topicName=PI3K)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/101296147/BF4BC9769C2FF12AC93CAA0069C0696C/100, createdBy=7bb22500091, createdName=ms1292405679162969, createdTime=Wed Apr 03 03:20:00 CST 2019, time=2019-04-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273300, encodeId=314f12e3300be, content=<a href='/topic/show?id=310d383ef5' target=_blank style='color:#2F92EE;'>#B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Wed Apr 03 03:20:00 CST 2019, time=2019-04-03, status=1, ipAttribution=)]
    2019-04-03 freve
  8. 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createdName=ms1292405679162969, createdTime=Wed Apr 03 03:20:00 CST 2019, time=2019-04-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1273300, encodeId=314f12e3300be, content=<a href='/topic/show?id=310d383ef5' target=_blank style='color:#2F92EE;'>#B细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3837, encryptionId=310d383ef5, topicName=B细胞)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6eba113, createdName=xiaoyeshuang, createdTime=Wed Apr 03 03:20:00 CST 2019, time=2019-04-03, status=1, ipAttribution=)]
    2019-04-03 yzh402
  9. 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  10. 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