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ECHO-301意外失败：IDO抑制剂类肿瘤免疫抑制剂路在何方？

2018-04-07 MedSci MedSci

IDO抑制剂ECHO
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今天万众瞩目的ECH-O301/Keynote-252试验因无效被提前终止。试验招募700多位无法手术的晚期恶性黑色素瘤病人，按PD-L1表达和BRAF突变分层，干预方法为Keytruda背景上加入IDO抑制剂Epacadostat，主要终点无进展生存期（PFS）和总生存期（OS）。今天公布的主要分析显示加入Epacadostat未能改善PFS（HR=1），改善OS的可能性也很小。因为IDO是PD

今天万众瞩目的ECH-O301/Keynote-252试验因无效被提前终止。试验招募700多位无法手术的晚期恶性黑色素瘤病人，按PD-L1表达和BRAF突变分层，干预方法为Keytruda背景上加入IDO抑制剂Epacadostat，主要终点无进展生存期（PFS）和总生存期（OS）。今天公布的主要分析显示加入Epacadostat未能改善PFS（HR=1），改善OS的可能性也很小。因为IDO是PD-1组合疗法的一个重要方向，这个失败不仅令Incyte下滑20%、默沙东下滑2%，也令多家开发IO组合的企业遭受不同程度打击。其中完全依靠IDO的Newlink下滑42%，开发所谓IDO2.0、选择性CD122激动剂的Nektar下滑近8%。全世界一片哗然，寄予厚望的免疫治疗联合使用，竟然失败了！



此前IDO+PD1的联用数据一路飘红：去年6月的ASCO2017大会上Incyte宣布epacadostat+ pembrolizumab治疗晚期NSCLC可使ORR和疾病控制率分别达到35%和63%；去年9月的ESMO2017大会上Incyte宣布I/II期ECHO-202（KEYNOTE-037）研究中epacadostat+ pembrolizumab可使晚期黑色素瘤患者的ORR达到56%；去年11月BMS公布的Opdivo联合自家IDO抑制剂BMS-986205的I/II期研究中，膀胱癌和宫颈癌队列患者也取得了积极结果。这一系列成功给人们IDO抑制剂联合PD-1/PD-L1以信心

尤其是I/II期ECHO-202研究（KEYNOTE-037研究）的临床数据。结果显示，所有患者（包括初治和经治患者）的ORR达到56%（35/63），完全缓解14%（9/63）；部分缓解41%（26/63），疾病稳定16%（10/63）。疾病控制率71%（45/63）。在所有35例产生应答的患者中，有30例在数据分析时仍维持缓解，中位缓解时间为45周（1+~121+周）。中位PFS为12.4个月；6个月时，疾病无进展的患者比例为65%；12个月时，疾病无进展的患者比例为52%；18个月时，疾病无进展的患者比例为49%。epacadostat各个剂量组（剂量递增25, 50, 100mg，bid）与Keytruda联用的效果一致。其中初治患者（一线治疗）黑色素瘤患者的mPFS高达22.8个月。ECHO-202研究可以说是大获成功！


ECHO-301（KEYNOTE-252）是一项随机、双盲、安慰剂对照研究，入组了706例不可手术切除或转移性黑色素瘤患者，按照1:1分组（根据PD-L1表达水平和BRAF突变状态和治疗情况对患者设置亚组），分别给予epacadostat + Keytruda或单独使用Keytruda。主要终点包括PFS和OS，次要终点包括ORR、安全性和耐受性。主要终点失败了。

IDO是过去5年制药工业最热门的未确证机理之一，理论是肿瘤利用这个酶的活性制造抑制免疫应答的犬尿氨酸。最早进入临床的是Newlink的NLG919，但这个药物并非IDO抑制剂、后来被包装成IDO通路抑制剂。Epac成为第一个真正的IDO抑制剂，前年在一个一/二期临床的恶黑亚组产生56%应答率，去年公布的长期跟踪结果显示PFS为22.8个月，这比单方使用Keytruda的历史数据更好（当然也远好于今天公布的ECHO301的11个月）。

梅斯医学小编认为，I/II期结果与III期结果差异如此巨大，这也反映了临床试验的不易。如果比较ECHO-202和ECHO-301，在ECHO-202中，共纳入65例患者，其中初治为54例，所有人群的PFS（不是主要终点）这12.4个月(6.2, 23.8)，但初治患者PFS为22.8个月(6.2, 23.8)，初治患者在获得6个月的病情稳定后，绝大多数患者都能持续稳定到18个月以上，这是给ECHO-301作为恶黑的一线治疗提供信心。但是，二者不同的是，其一，ECHO-202样本量小，其中一线治疗仅54例，其二，地区不一样，ECHO-202在美国进行，而ECHO-301在全球进行，其三，ECHO-202评价PFS是次要终点，在患者获得ORR后，是否存在后续治疗？这些都有可能是偏倚。直接把I/II期结果迅速推广到III期，还是缺乏冷静，也可能是被胜利冲晕了头脑。可能是I/II期结果给予过高信心和期望，使得III期结果被认为是理所当然的阳性结果。就研究设计本身而言，可能过于冒进，毕竟，我们对IDO的认知还十分肤浅，抑或是对于恶性黑色素瘤而言，Keytruda已足够的好，掩盖掉IDO类药物的作用。如果是前者，那么后面一系列的免疫治疗联用试验都可能面临危机，需要深入研究IDO的相关biomarker后，才有可能真正了解什么样的人群是IDO抑制剂的适合人群。如果是后者，在其它肿瘤中，成功概率是很大的，毕竟在其它肿瘤中，Keytruda表现虽然很优异，但并不是十分完美。而且除黑色素瘤，膀胱癌这类对免疫敏感性肿瘤外，其它肿瘤（如肺癌，乳腺癌，胃癌等），PD-1/PD-L1依然只是选择之一，还有很大的提升空间，免疫治疗联用策略，应该是令人期许的。

ECHO-202详细结果：



当然，ECHO-301失败，并不意味着结束，还有很多试验在路上，人类的探索也不会停止。

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    2023-05-10 侠胆医心 来自上海

    #Epacadostat#+ #Pembrolizumab#治疗晚期#NSCLC#可使ORR和疾病控制率分别达到35%和63%；去年9月的ESMO2017大会上Incyte宣布I/II期ECHO-202（KEYNOTE-037）研究中epacadostat+ pembrolizumab可使晚期#黑色素瘤#患者的ORR达到56%；去年11月BMS公布的Opdivo联合自家#IDO抑制剂##BMS-986205#的I/II期研究中，#膀胱癌#和#宫颈癌#队列患者也取得了积极结果。 但三期失败，不过，最近文献来看，在#胶质母细胞瘤#可能#IDO1#仍然有相当的潜力！！

    0

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    2018-04-19 jklm09

    #抑制剂#

    0

  3. [GetPortalCommentsPageByObjectIdResponse(id=2131311, encodeId=ec942131311a6, content=<a href='/topic/show?id=2ca46852d7' target=_blank style='color:#2F92EE;'>#Epacadostat#</a>+ <a href='/topic/show?id=4323140286a' target=_blank style='color:#2F92EE;'>#Pembrolizumab#</a>治疗晚期<a href='/topic/show?id=2493130e1a1' target=_blank style='color:#2F92EE;'>#NSCLC#</a>可使ORR和疾病控制率分别达到35%和63%；去年9月的ESMO2017大会上Incyte宣布I/II期ECHO-202（KEYNOTE-037）研究中epacadostat+ pembrolizumab可使晚期<a href='/topic/show?id=330410333110' target=_blank style='color:#2F92EE;'>#黑色素瘤#</a>患者的ORR达到56%；去年11月BMS公布的Opdivo联合自家<a href='/topic/show?id=9517942978' target=_blank style='color:#2F92EE;'>#IDO抑制剂#</a><a href='/topic/show?id=6cd310620285' target=_blank style='color:#2F92EE;'>#BMS-986205#</a>的I/II期研究中，<a href='/topic/show?id=843a85e9421' target=_blank style='color:#2F92EE;'>#膀胱癌#</a>和<a href='/topic/show?id=146246308d1' target=_blank style='color:#2F92EE;'>#宫颈癌#</a>队列患者也取得了积极结果。 但三期失败，不过，最近文献来看，在<a href='/topic/show?id=01858406438' target=_blank style='color:#2F92EE;'>#胶质母细胞瘤#</a>可能<a href='/topic/show?id=2853942e78' target=_blank style='color:#2F92EE;'>#IDO1#</a>仍然有相当的潜力！！, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6852, encryptionId=2ca46852d7, topicName=Epacadostat), TopicDto(id=14028, encryptionId=4323140286a, topicName=Pembrolizumab), TopicDto(id=13071, encryptionId=2493130e1a1, topicName=NSCLC), TopicDto(id=103331, encryptionId=330410333110, topicName=黑色素瘤), TopicDto(id=9429, encryptionId=9517942978, topicName=IDO抑制剂), TopicDto(id=106202, encryptionId=6cd310620285, topicName=BMS-986205), TopicDto(id=85794, encryptionId=843a85e9421, topicName=膀胱癌), TopicDto(id=46308, encryptionId=146246308d1, topicName=宫颈癌), TopicDto(id=84064, encryptionId=01858406438, topicName=胶质母细胞瘤), TopicDto(id=9427, encryptionId=2853942e78, topicName=IDO1)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/Random/55971dc507c93968175ce7cc1e177b372a83869f.jpg, createdBy=f63e4754896, createdName=侠胆医心, createdTime=Wed May 10 07:36:23 CST 2023, time=2023-05-10, status=1, ipAttribution=上海), GetPortalCommentsPageByObjectIdResponse(id=1851684, encodeId=ff3f1851684c0, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Thu Apr 19 11:18:00 CST 2018, time=2018-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1715769, encodeId=61f11e15769d9, content=<a href='/topic/show?id=9517942978' target=_blank style='color:#2F92EE;'>#IDO抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9429, encryptionId=9517942978, topicName=IDO抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1ea832038829, createdName=bshuang, createdTime=Sun Aug 12 12:18:00 CST 2018, time=2018-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1703509, encodeId=e3091e03509c8, content=<a href='/topic/show?id=327e9425fc' target=_blank style='color:#2F92EE;'>#IDO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9425, encryptionId=327e9425fc, topicName=IDO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3e3a30514791, createdName=tongyongming, createdTime=Sat Apr 21 18:18:00 CST 2018, time=2018-04-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1286277, encodeId=141512862e7f1, content=<a href='/topic/show?id=d65b290333d' target=_blank style='color:#2F92EE;'>#免疫抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29033, encryptionId=d65b290333d, topicName=免疫抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=010d202, createdName=amy0550, createdTime=Mon Apr 09 00:18:00 CST 2018, time=2018-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=303879, encodeId=b8b83038e925, content=学习了很多先进水平, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161027/IMG58114E1818EA51495.jpg, createdBy=4b2c1959822, createdName=雅文博武, createdTime=Sun Apr 08 11:22:27 CST 2018, time=2018-04-08, status=1, ipAttribution=)]
    2018-08-12 bshuang

    #IDO抑制剂#

    0

  4. [GetPortalCommentsPageByObjectIdResponse(id=2131311, encodeId=ec942131311a6, content=<a href='/topic/show?id=2ca46852d7' target=_blank style='color:#2F92EE;'>#Epacadostat#</a>+ <a href='/topic/show?id=4323140286a' target=_blank style='color:#2F92EE;'>#Pembrolizumab#</a>治疗晚期<a href='/topic/show?id=2493130e1a1' target=_blank style='color:#2F92EE;'>#NSCLC#</a>可使ORR和疾病控制率分别达到35%和63%；去年9月的ESMO2017大会上Incyte宣布I/II期ECHO-202（KEYNOTE-037）研究中epacadostat+ pembrolizumab可使晚期<a href='/topic/show?id=330410333110' target=_blank style='color:#2F92EE;'>#黑色素瘤#</a>患者的ORR达到56%；去年11月BMS公布的Opdivo联合自家<a href='/topic/show?id=9517942978' target=_blank style='color:#2F92EE;'>#IDO抑制剂#</a><a href='/topic/show?id=6cd310620285' target=_blank style='color:#2F92EE;'>#BMS-986205#</a>的I/II期研究中，<a href='/topic/show?id=843a85e9421' target=_blank style='color:#2F92EE;'>#膀胱癌#</a>和<a href='/topic/show?id=146246308d1' target=_blank style='color:#2F92EE;'>#宫颈癌#</a>队列患者也取得了积极结果。 但三期失败，不过，最近文献来看，在<a href='/topic/show?id=01858406438' target=_blank style='color:#2F92EE;'>#胶质母细胞瘤#</a>可能<a href='/topic/show?id=2853942e78' target=_blank style='color:#2F92EE;'>#IDO1#</a>仍然有相当的潜力！！, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6852, encryptionId=2ca46852d7, topicName=Epacadostat), TopicDto(id=14028, encryptionId=4323140286a, topicName=Pembrolizumab), TopicDto(id=13071, encryptionId=2493130e1a1, topicName=NSCLC), TopicDto(id=103331, encryptionId=330410333110, topicName=黑色素瘤), TopicDto(id=9429, encryptionId=9517942978, topicName=IDO抑制剂), TopicDto(id=106202, encryptionId=6cd310620285, topicName=BMS-986205), TopicDto(id=85794, encryptionId=843a85e9421, topicName=膀胱癌), TopicDto(id=46308, encryptionId=146246308d1, topicName=宫颈癌), TopicDto(id=84064, encryptionId=01858406438, topicName=胶质母细胞瘤), TopicDto(id=9427, encryptionId=2853942e78, topicName=IDO1)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/Random/55971dc507c93968175ce7cc1e177b372a83869f.jpg, createdBy=f63e4754896, createdName=侠胆医心, createdTime=Wed May 10 07:36:23 CST 2023, time=2023-05-10, status=1, ipAttribution=上海), GetPortalCommentsPageByObjectIdResponse(id=1851684, encodeId=ff3f1851684c0, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Thu Apr 19 11:18:00 CST 2018, time=2018-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1715769, encodeId=61f11e15769d9, content=<a href='/topic/show?id=9517942978' target=_blank style='color:#2F92EE;'>#IDO抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9429, encryptionId=9517942978, topicName=IDO抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1ea832038829, createdName=bshuang, createdTime=Sun Aug 12 12:18:00 CST 2018, time=2018-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1703509, encodeId=e3091e03509c8, content=<a href='/topic/show?id=327e9425fc' target=_blank style='color:#2F92EE;'>#IDO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9425, encryptionId=327e9425fc, topicName=IDO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3e3a30514791, createdName=tongyongming, createdTime=Sat Apr 21 18:18:00 CST 2018, time=2018-04-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1286277, encodeId=141512862e7f1, content=<a href='/topic/show?id=d65b290333d' target=_blank style='color:#2F92EE;'>#免疫抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29033, encryptionId=d65b290333d, topicName=免疫抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=010d202, createdName=amy0550, createdTime=Mon Apr 09 00:18:00 CST 2018, time=2018-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=303879, encodeId=b8b83038e925, content=学习了很多先进水平, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161027/IMG58114E1818EA51495.jpg, createdBy=4b2c1959822, createdName=雅文博武, createdTime=Sun Apr 08 11:22:27 CST 2018, time=2018-04-08, status=1, ipAttribution=)]
    2018-04-21 tongyongming

    #IDO#

    0

  5. [GetPortalCommentsPageByObjectIdResponse(id=2131311, encodeId=ec942131311a6, content=<a href='/topic/show?id=2ca46852d7' target=_blank style='color:#2F92EE;'>#Epacadostat#</a>+ <a href='/topic/show?id=4323140286a' target=_blank style='color:#2F92EE;'>#Pembrolizumab#</a>治疗晚期<a href='/topic/show?id=2493130e1a1' target=_blank style='color:#2F92EE;'>#NSCLC#</a>可使ORR和疾病控制率分别达到35%和63%；去年9月的ESMO2017大会上Incyte宣布I/II期ECHO-202（KEYNOTE-037）研究中epacadostat+ pembrolizumab可使晚期<a href='/topic/show?id=330410333110' target=_blank style='color:#2F92EE;'>#黑色素瘤#</a>患者的ORR达到56%；去年11月BMS公布的Opdivo联合自家<a href='/topic/show?id=9517942978' target=_blank style='color:#2F92EE;'>#IDO抑制剂#</a><a href='/topic/show?id=6cd310620285' target=_blank style='color:#2F92EE;'>#BMS-986205#</a>的I/II期研究中，<a href='/topic/show?id=843a85e9421' target=_blank style='color:#2F92EE;'>#膀胱癌#</a>和<a href='/topic/show?id=146246308d1' target=_blank style='color:#2F92EE;'>#宫颈癌#</a>队列患者也取得了积极结果。 但三期失败，不过，最近文献来看，在<a href='/topic/show?id=01858406438' target=_blank style='color:#2F92EE;'>#胶质母细胞瘤#</a>可能<a href='/topic/show?id=2853942e78' target=_blank style='color:#2F92EE;'>#IDO1#</a>仍然有相当的潜力！！, beContent=null, objectType=article, channel=null, level=null, likeNumber=83, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=6852, encryptionId=2ca46852d7, topicName=Epacadostat), TopicDto(id=14028, encryptionId=4323140286a, topicName=Pembrolizumab), TopicDto(id=13071, encryptionId=2493130e1a1, topicName=NSCLC), TopicDto(id=103331, encryptionId=330410333110, topicName=黑色素瘤), TopicDto(id=9429, encryptionId=9517942978, topicName=IDO抑制剂), TopicDto(id=106202, encryptionId=6cd310620285, topicName=BMS-986205), TopicDto(id=85794, encryptionId=843a85e9421, topicName=膀胱癌), TopicDto(id=46308, encryptionId=146246308d1, topicName=宫颈癌), TopicDto(id=84064, encryptionId=01858406438, topicName=胶质母细胞瘤), TopicDto(id=9427, encryptionId=2853942e78, topicName=IDO1)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/Random/55971dc507c93968175ce7cc1e177b372a83869f.jpg, createdBy=f63e4754896, createdName=侠胆医心, createdTime=Wed May 10 07:36:23 CST 2023, time=2023-05-10, status=1, ipAttribution=上海), GetPortalCommentsPageByObjectIdResponse(id=1851684, encodeId=ff3f1851684c0, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Thu Apr 19 11:18:00 CST 2018, time=2018-04-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1715769, encodeId=61f11e15769d9, content=<a href='/topic/show?id=9517942978' target=_blank style='color:#2F92EE;'>#IDO抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9429, encryptionId=9517942978, topicName=IDO抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=1ea832038829, createdName=bshuang, createdTime=Sun Aug 12 12:18:00 CST 2018, time=2018-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1703509, encodeId=e3091e03509c8, content=<a href='/topic/show?id=327e9425fc' target=_blank style='color:#2F92EE;'>#IDO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=35, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9425, encryptionId=327e9425fc, topicName=IDO)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=3e3a30514791, createdName=tongyongming, createdTime=Sat Apr 21 18:18:00 CST 2018, time=2018-04-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1286277, encodeId=141512862e7f1, content=<a href='/topic/show?id=d65b290333d' target=_blank style='color:#2F92EE;'>#免疫抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=29033, encryptionId=d65b290333d, topicName=免疫抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=010d202, createdName=amy0550, createdTime=Mon Apr 09 00:18:00 CST 2018, time=2018-04-09, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=303879, encodeId=b8b83038e925, content=学习了很多先进水平, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161027/IMG58114E1818EA51495.jpg, createdBy=4b2c1959822, createdName=雅文博武, createdTime=Sun Apr 08 11:22:27 CST 2018, time=2018-04-08, status=1, ipAttribution=)]
    2018-04-09 amy0550

    #免疫抑制剂#

    0

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    2018-04-08 雅文博武

    学习了很多先进水平

    0

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