Oncology Frontier: Could you outline the effective treatment approach after TKI failures?

　　《肿瘤瞭望》：请谈一谈TKI治疗失败CML的有效治疗方法。

　　Dr Radich: For primary failures， the usual scenario is where patients are using imatinib and need to change to a second-generation drug. If you have clearly failed imatinib (about 50% of patients get a complete molecular response (CMR))then you move on to nilotinib or dasatinib. So for that that 50% that don’t respond， there are alternative therapies in those cases. In some cases there are third-line agents like bosutinib and omacetaxine as well as transplantation， which we know are very effective treatments for this disease. So if people fail front-line therapy， it is perfectly logical to put them on a second-line of therapy but if those patients are transplant candidates， then we need to keep that in mind if they are one of the unlucky half that don’t respond to second-line therapy.

　　Radich博士：对于初级治疗失败的患者，其先前用药通常是伊马替尼，则需要换成第二代TKI。如果伊马替尼治疗完全失败（约50%的患者获得完全分子反应，CMR），那么换成尼洛替尼或达沙替尼治疗，即余下的50%没有效果的患者有其替代疗法。在某些情况下，也有三线治疗选择“波舒替尼和高三尖杉酯碱（omacetaxine）以及移植”，这些方法可有效治疗耐药性CML。因此，一线治疗失败则进行二线治疗；如果患者适合移植治疗，若其二线治疗失败，医生则考虑给予移植治疗。

　　Oncology Frontier:  Is it possible to stop CML therapy after achieving CMR?

　　《肿瘤瞭望》：如果CML患者获得了CMR，能否停止CML治疗？

　　Dr Radich: There is a huge amount of interest now in the discontinuation of therapy. There was some shock a few years ago when we discovered that people who had had a complete molecular response for several years (and at least two years) were taken off these drugs and most of those patients (60%) relapsed within the first six months. But 40% of them stayed CMR after two years of follow-up， which is really quite remarkable. We don’t know if there is any downside to discontinuation， because all of the patients who relapsed after discontinuation have responded again back on therapy. But we don’t know if there is an indication or timing for discontinuing therapy that set them up to progress again years down the line. We are currently looking at this in a clinical trial but I think this is a very important feature because if it is successful then we can start looking at treating younger patients especially very aggressively with the idea of driving them into CMR and eventually getting them off the drug.

　　Radich博士：对CML患者停药的研究是目前研究热点，几年前的研究结果令人震惊，研究中的患者已获得CMR数年（至少两年），停药后六个月内60％的患者复发；40%的患者在随访两年后继续保存CMR，这一结果相当显着。目前还不清楚停药是否有不利的一面，但所有停药后复发的患者再次治疗依然有效。目前尚不知晓CML停药指证或时间点，目前正在进行临床试验研究这个问题，如果试验研究成功，则可开始探索较年轻CML患者的停药策略——使年轻患者获得CMR并最终实现停药。