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[ICML巅峰访谈] 新药时代下,慢性淋巴细胞白血病治疗前瞻

作者:肿瘤瞭望   日期:2017/6/19 15:13:30  浏览量:24986

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编者按:慢性淋巴细胞白血病(CLL)是一种高度异质性的慢性B淋巴细胞克隆增殖性疾病。近年来,随着化学免疫、BCL-2抑制剂、BCR信号通路抑制剂、PD-1抑制剂和嵌合抗原受体的T细胞(CAR-T)等新型药物及治疗方法不断涌现,CLL的治疗效果和缓解程度不断提高。在第14届Lugano国际淋巴瘤大会(ICML)上,本刊特邀请德国科隆大学M. Hallek教授分享了关于新药时代下,CLL治疗的热点话题。


《肿瘤瞭望》:请您从整体上谈一谈近年来出现的CLL新药治疗?
 
Hallek教授:在慢性淋巴细胞白血病领域,我们已经看到在新药研发上有了许多进展。目前,已有4种药物获批在临床上应用,显示出非常重要的地位,它们分别是:①obinutuzumab,为一种新型的抗-CD20抗体,相较于利妥昔单抗具有更佳疗效;②venetoclax,为新近获批的BCL-2 拮抗剂,其单药治疗与联合治疗效果非常显著;③ ibrutinib,为一种新型的酪氨酸激酶抑制剂(BTK);④idelalisib,PI3Kδ抑制剂,抑制BCR信号通路以及CXCR4、CXCR5信号,诱导B细胞凋亡,抑制B细胞增殖。通过本届ICML大会以及今年其他会议,我们可以看到上述新药对于CLL联合治疗的广泛应用前景:不仅可获得治疗应答率的提升,而且可获得更高的完全缓解率、以及更深的分子学缓解。这些激动人心的进步将进一步使CLL患者获得更好的生存。
 
《肿瘤瞭望》:本届ICML大会在CLL领域有哪些亮点内容?
 
Hallek教授:本届ICML大会上亮点颇多,如果说从个人角度推荐最感兴趣的研究,我认为首先是新的靶向治疗药物的联合应用。随着多种新型TKI药物的问世,一种新型BTK抑制剂与抗体药物的联合显示出良好的疗效。其次,关于抗-CD20抗体+ idelalisib + ibrutinib的三联治疗在多种类型的淋巴瘤患者(包括滤泡性淋巴瘤、慢性淋巴细胞白血病)中取得了显著的治疗应答率。最后,我们研究小组的一项数据表明,采用bendamustine +venetoclax + obinutuzumab序贯治疗慢性淋巴细胞白血病患者,在一线治疗中可以获得90%以上的微小残留病灶阴性的治疗效果,在二线治疗中可超过80%。既往,以FCR为一线的化学免疫治疗可获得66%的缓解,现今通过新药的联合可获得90%以上的缓解。随着新的数据不断涌现,如果无疾病生存期能足够延长,慢性淋巴细胞白血病患者将更加接近治愈,从而进入一个崭新的时代。当然,CLL是否能够实现治愈我们目前还不能作出论断,我们必须谨慎等待更长的随访研究结果。以上是我认为本届ICML大会在慢性淋巴细胞白血病领域呈现最重要的信息。

阅读原文链接:
 
Oncology Frontier: Can you tell us about the new drugs for chronic lymphocytic leukemia (CLL) treatment?
 
Dr Hallek: In CLL, we have recently seen exciting developments in new agents. There are four that have been registered and are very important. They are: obinutuzumab, an anti-CD20 antibody engineered by GlycArt, that has more efficacy than rituximab; the BCL-2 antagonist venetoclax that has recently been approved and is a highly efficient single agent already, and even more impressive in combination; next is ibrutinib, which has BTK inhibiting activity and is also a single agent with impressive activity; and finally, idelalisib, a PI3K-delta inhibitor that also shows very good activity. What we have learned at this meeting and other meetings this year is that the full potential of these agents comes from combining them. Response rates increase, we achieve more complete remissions and we achieve more molecular remissions with these agents in CLL when properly combined. These are exciting times in chronic lymphocytic leukemia.
 
Oncology Frontier: What topics have interested you the most at this meeting?
 
Dr Hallek: Overall, the most interesting data that I would cite from presentations given here at the meeting are firstly, combinations of novel inhibitors. There is a new BTK inhibitor from a company called BeiGene combined with antibodies that is showing interesting activity. There has been a triple combination with an anti-CD20 antibody plus a PI3K inhibitor plus ibrutinib again showing very impressive response rates in various lymphomas including follicular lymphoma and CLL. Finally, there is data from my own group presented at the Plenary Session by Paula Cramer from the German CLL Study Group (GCLLSG) showing a sequential combination of bendamustine and venetoclax plus obinutuzumab with MRD-negative remissions in more than 90% of first-line treated patients and more than 80% of second-line treated patients. These are new observations that may get close to the eradication of CLL if these remissions are lasting. It is a new step. With FCR in the first-line, we have reached 66% remission with chemo-immunotherapy, and now with these novel agents, we are achieving 90% and more. That opens the door to the potential for achieving long-lasting remissions in the majority of patients with CLL. Whether that will equate to a cure or not, we cannot say. We have to be careful and wait for longer follow-up data. These are the most impressive pieces of information from this meeting.

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