: According to a study published  February 11 in Lancet Oncology， lenalidomide increases the risk for hematologic second primary malignancies. However， the risk appears to be primarily driven by co-exposure to melphalan. What’s your comment on this finding?

　　《肿瘤瞭望》：根据Lancet Oncology 2月11号发布的一篇临床试验声称，来那度胺可以增加多发性骨髓瘤治疗过程中血液系统第二原发恶性肿瘤的发生风险，这种风险可能主要与马法兰的联合使用有关，对此您怎么看？

　　Dr Bergsagel: There is pretty clear data from randomized studies for people who received lenalidomide， almost always after they had received melphalan， that shows that it is associated with an increased risk of second primary malignancies. But there are some more recent studies， particularly looking at newly diagnosed patients who have never seen melphalan and have only seen lenalidomide and there is no increased risk whatsoever in that setting. So it appears that exposure to melphalan and probably other DNA-damaging agents predisposes to the mechanism. However， it is worth noting that a new function of lenalidomide has been described of degrading Ikaros. Ikaros is a tumor-suppressor gene for acute leukemia. So there is a rationale for why lenalidomide would be associated with increased incidence of acute lymphoblastic leukemia (ALL) in particular.

　　Bergsagel博士：对使用马法兰之后用来那度胺治疗的多发性骨髓瘤患者进行随机试验得到的可观数据表明马法兰的联合使用与血液系统第二原发恶性肿瘤的发生风险增加有关。有一些更新的研究显示，那些没有用马法兰只使用来那度胺的初次治疗患者，患病风险并没有增加。这样看来，马法兰和其他DNA损伤剂可能容易诱发第二原发恶性肿瘤。然而，值得注意的是，来那度胺的一种新功能被发现，它能降解伊卡洛斯。伊卡洛斯是一种急性白血病的肿瘤抑制基因。因此这可能是来那度胺与急性淋巴细胞白血病（ALL）发病率增加相关的原因。

　　: Recently， a modified measles virus produced complete remission at all tumor sites in a heavily pre-treated patient with myeloma， as reported in a phase I clinical trial in Mayo Clinic Proceedings. It seems to be a landmark study. What’s your opinion about this trial?

　　《肿瘤瞭望》：近日梅奥诊所公布了一例既往接受过多次治疗的多发性骨髓瘤患者在接受超高剂量的改良型麻疹病毒治疗后全身肿瘤完全缓解的一期临床试验结果，外界普遍认为这是一个具有里程碑意义的发现，对此您的看法是？

　　Dr Bergsagel: That’s the pioneering work of Stephen Russell at the Mayo Clinic in Rochester and something he has been working on for years. It is obviously quite complicated to manufacture the virus and get approval and he had to start at a very low titer of the virus. The idea is that this modified measles virus is different from the measles virus and only infects certain cells that express a receptor called CD46. As it turns out myeloma expresses a lot of this receptor and so is infected by the virus and replicates and kills the tumor cells， oncolysis. Quite marked responses have been seen now in two patients and I think it is going to open up a whole new therapy. It is nice to think about a virus that replicates in an exponential-type therapy against a tumor that has exponential growth.

　　Bergsagel博士：这是斯蒂芬·拉塞尔在罗切斯特梅奥诊所的开创性工作，他多年来一直致力于此。显然，制造病毒并获得批准是相当难办的，他不得不以非常低的病毒滴度开始。他想制造与麻疹病毒不同的改良型麻疹病毒，改病毒只能感染表达CD46受体的特定细胞。事实证明骨髓瘤表达大量CD46受体，因此改良型麻疹病毒感染骨髓瘤细胞，病毒复制并杀死肿瘤细胞，即溶瘤。目前在两位患者身上已经观察到相当显著的反应效果，我认为这将开辟一种全新疗法。用病毒指数型复制疗法对抗肿瘤的指数型增长，是值得期待的。