Blood:T细胞淋巴瘤患者采用鲁索替尼靶向抑制JAK/STAT的临床获益情况

2022-01-07 Nebula MedSci原创

外周 T 细胞淋巴瘤患者或可采用靶向 JAK/STAT 抑制的精确治疗策略

外周 T 细胞淋巴瘤 (PTCL) )和非真蕈样真菌病 (非MF) 皮肤 T 细胞淋巴瘤 (CTCL) 是一类具有明显异质性的疾病,其特征是初始治疗的治愈率相对较低,复发或难治性疾病的选择有限。迄今为止,还没有获批用于治疗 PTCL 的口服疗法,而且还迫切需要更好的治疗复发或难治性 PTCL 的方案。

通过 JAK1 和/或 JAK2 的信号传导在外周 T 细胞淋巴瘤 (PTCL) 的肿瘤和非肿瘤细胞中均很常见。因此,靶向 JAK 信号通路或可为 PTCL 的治疗带来新的希望。

本研究是一项关于复发或难治性 PTCL(n=45)或蕈样真菌病(n=7)患者采用 JAK1/2 抑制剂鲁索替尼治疗的 2 期研究。根据生物标志物,受试患者被分到了三个队列:1)激活性JAK和/或 STAT 突变;2)在肿瘤细胞中有 ≥30% 的 pSTAT3 表达;3)无和不足以评估的组织。受试患者每天接受两次鲁索替尼 20mg 直到病情进展,在第2个疗程、第5个疗程以及随后每3个疗程评估一次治疗反应。主要终点是临床获益率(CBR),即完全缓解、客观缓解和疾病稳定超过6个月的总和。

不同队列和亚型的临床获益情况

7位 MF 患者中只有 1 位有临床获益(客观缓解>18个月)。在队列 1、2、3 的 PTCL 病例(n=45)中,CBR 率分别是53%、45%和13%(队列2/3与队列1相比,p=0.02)。有 8 位患者的临床获益持续超过了 12 个月,其中 4 位是 T 细胞大颗粒淋巴细胞白血病(总的有 5 位)。

不同队列的PTCL患者的治疗效果

在使用多重免疫荧光进行的探索性分析中,磷酸化 S6(一种 PI3 激酶或丝裂原活化蛋白激酶激活的标志物)的表达在 <25% 的肿瘤细胞中与对鲁索替尼治疗的反应性相关(p=0.05)。

总之,该研究表明,鲁索替尼在各种 PTCL 亚型中均具有抗肿瘤活性,提示 PTCL 患者或可采用对 JAK/STAT 抑制的精确治疗策略。

原始出处:

Alison J. Moskowitz, et al. A phase 2 biomarker-driven study of ruxolitinib demonstrates effectiveness of JAK/STAT targeting in T-cell lymphomas. Blood (2021) 138 (26): 2828–2837.

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (4)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=2040411, encodeId=dc1d2040411f1, content=<a href='/topic/show?id=1f61229925d' target=_blank style='color:#2F92EE;'>#临床获益#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22992, encryptionId=1f61229925d, topicName=临床获益)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Tue Dec 06 02:14:43 CST 2022, time=2022-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1738064, encodeId=aa5a1e3806440, content=<a href='/topic/show?id=0abd10215e0' target=_blank style='color:#2F92EE;'>#JAK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10215, encryptionId=0abd10215e0, topicName=JAK)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e8634348903, createdName=肉我只吃一口, createdTime=Thu Nov 10 15:14:43 CST 2022, time=2022-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1702701, encodeId=b1fa1e02701d0, content=<a href='/topic/show?id=ddc9e795159' target=_blank style='color:#2F92EE;'>#细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77951, encryptionId=ddc9e795159, topicName=细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=201630414353, createdName=marlenexl, createdTime=Fri Jul 29 13:14:43 CST 2022, time=2022-07-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372692, encodeId=f96c13e2692bb, content=<a href='/topic/show?id=7d2d1802820' target=_blank style='color:#2F92EE;'>#T细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18028, encryptionId=7d2d1802820, topicName=T细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bfa6343, createdName=aliceclz, createdTime=Sun Jan 09 06:14:43 CST 2022, time=2022-01-09, status=1, ipAttribution=)]
  2. [GetPortalCommentsPageByObjectIdResponse(id=2040411, encodeId=dc1d2040411f1, content=<a href='/topic/show?id=1f61229925d' target=_blank style='color:#2F92EE;'>#临床获益#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22992, encryptionId=1f61229925d, topicName=临床获益)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Tue Dec 06 02:14:43 CST 2022, time=2022-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1738064, encodeId=aa5a1e3806440, content=<a href='/topic/show?id=0abd10215e0' target=_blank style='color:#2F92EE;'>#JAK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10215, encryptionId=0abd10215e0, topicName=JAK)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e8634348903, createdName=肉我只吃一口, createdTime=Thu Nov 10 15:14:43 CST 2022, time=2022-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1702701, encodeId=b1fa1e02701d0, content=<a href='/topic/show?id=ddc9e795159' target=_blank style='color:#2F92EE;'>#细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77951, encryptionId=ddc9e795159, topicName=细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=201630414353, createdName=marlenexl, createdTime=Fri Jul 29 13:14:43 CST 2022, time=2022-07-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372692, encodeId=f96c13e2692bb, content=<a href='/topic/show?id=7d2d1802820' target=_blank style='color:#2F92EE;'>#T细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18028, encryptionId=7d2d1802820, topicName=T细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bfa6343, createdName=aliceclz, createdTime=Sun Jan 09 06:14:43 CST 2022, time=2022-01-09, status=1, ipAttribution=)]
  3. [GetPortalCommentsPageByObjectIdResponse(id=2040411, encodeId=dc1d2040411f1, content=<a href='/topic/show?id=1f61229925d' target=_blank style='color:#2F92EE;'>#临床获益#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22992, encryptionId=1f61229925d, topicName=临床获益)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Tue Dec 06 02:14:43 CST 2022, time=2022-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1738064, encodeId=aa5a1e3806440, content=<a href='/topic/show?id=0abd10215e0' target=_blank style='color:#2F92EE;'>#JAK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10215, encryptionId=0abd10215e0, topicName=JAK)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e8634348903, createdName=肉我只吃一口, createdTime=Thu Nov 10 15:14:43 CST 2022, time=2022-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1702701, encodeId=b1fa1e02701d0, content=<a href='/topic/show?id=ddc9e795159' target=_blank style='color:#2F92EE;'>#细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77951, encryptionId=ddc9e795159, topicName=细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=201630414353, createdName=marlenexl, createdTime=Fri Jul 29 13:14:43 CST 2022, time=2022-07-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372692, encodeId=f96c13e2692bb, content=<a href='/topic/show?id=7d2d1802820' target=_blank style='color:#2F92EE;'>#T细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18028, encryptionId=7d2d1802820, topicName=T细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bfa6343, createdName=aliceclz, createdTime=Sun Jan 09 06:14:43 CST 2022, time=2022-01-09, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=2040411, encodeId=dc1d2040411f1, content=<a href='/topic/show?id=1f61229925d' target=_blank style='color:#2F92EE;'>#临床获益#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=28, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=22992, encryptionId=1f61229925d, topicName=临床获益)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=21015, createdName=heli0118, createdTime=Tue Dec 06 02:14:43 CST 2022, time=2022-12-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1738064, encodeId=aa5a1e3806440, content=<a href='/topic/show?id=0abd10215e0' target=_blank style='color:#2F92EE;'>#JAK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10215, encryptionId=0abd10215e0, topicName=JAK)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e8634348903, createdName=肉我只吃一口, createdTime=Thu Nov 10 15:14:43 CST 2022, time=2022-11-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1702701, encodeId=b1fa1e02701d0, content=<a href='/topic/show?id=ddc9e795159' target=_blank style='color:#2F92EE;'>#细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77951, encryptionId=ddc9e795159, topicName=细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=201630414353, createdName=marlenexl, createdTime=Fri Jul 29 13:14:43 CST 2022, time=2022-07-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1372692, encodeId=f96c13e2692bb, content=<a href='/topic/show?id=7d2d1802820' target=_blank style='color:#2F92EE;'>#T细胞淋巴瘤#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18028, encryptionId=7d2d1802820, topicName=T细胞淋巴瘤)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=bfa6343, createdName=aliceclz, createdTime=Sun Jan 09 06:14:43 CST 2022, time=2022-01-09, status=1, ipAttribution=)]

相关资讯

FDA接受ST-001 nanoFenretinide治疗T细胞淋巴瘤的新药申请

美国FDA已接受SciTech Development公司的ST-001 nanoFenretinide的试验性新药(IND)申请,这是一种T细胞非霍奇金淋巴瘤(NHL)的实验性治疗方法。

NCCN临床实践指南:T细胞淋巴瘤(2020.V1)

2020年1月,美国国家综合癌症网络(NCCN)发布了T细胞淋巴瘤指南2020年第1版,指南主要内容包括: 指南更新摘要 外周T细胞性淋巴瘤 乳腺植入物相关的间变性大细胞淋巴瘤 蕈样真菌病/Sezary综合症 原发性皮肤CD30+T细胞淋巴增殖性疾病 T细胞大颗粒淋巴细胞白血病 成人T细胞白血病/淋巴瘤 T细胞造血干细胞白血病 淋巴结外侵犯NK / T细胞淋巴瘤,鼻型 维持治疗 非霍奇金淋巴瘤卢加

J Dermatolog Treat:多西环素治疗早期真菌病的疗效

蕈样真菌病(MF)是原发性皮肤T细胞淋巴瘤(CTCLs)的最常见形式。多西环素是四环素类抗生素中的一种,能促进不同人类恶性细胞系和体内模型的细胞凋亡。

Mallinckrodt的UVADEX(甲氧沙林)获得澳大利亚批准,与THERAKOS CELLEX光电穿刺系统联合治疗成人慢性移植物抗宿主疾病和T细胞淋巴瘤

Mallinckrodt公司宣布,UVADEX(甲氧沙林)获得澳大利亚管理局(TGA)批准,与THERAKOS CELLEX光电穿刺系统联合,用于同种异体造血干细胞(HSC)移植后类固醇难治和类固醇不耐受的慢性移植物抗宿主病(cGvHD)。TGA还批准了Uvadex与THERAKOS CELLEX 光电穿刺系统联合用于姑息治疗对其他治疗无反应的皮肤T细胞淋巴瘤(CTCL)的皮肤症状。

Cell Death Dis:他汀类药物在p53突变型T型淋巴瘤中的抗癌作用

长期以来的研究发现他汀类药物可能具有抗肿瘤活性。目前一些流行病学的证据显示,他汀类药物的使用与许多散发性癌症(包括大肠癌、乳腺癌、肺癌、前列腺癌和肾癌)的死亡率降低息息相关。

miR-155抑制剂治疗T细胞淋巴瘤,获得美国FDA的孤儿药物指定

microRNA-155的过表达与多种T细胞淋巴瘤和其他血液癌的预后不良有关。