编者按：老年急性淋巴细胞白血病（ALL）是临床不容忽视的群体，具有高Ph（+）、高甲基化、高发分子学异常等特点，临床治疗手段较成人和儿童患者少得多。酪氨酸激酶抑制剂的出现大大改变了Ph（+）ALL患者的治疗现状，其与其他手段联合使用有望进一步提高老年ALL患者的完全缓解率和总体生存。然而老年患者其体质原因在治疗过程中因对药物耐受能力差，具有一定的治疗风险，如何平衡风险和受益仍有待我们进一步临床研究。在本届ASCO年会上英国布里斯托尔大学医院David I. Marks教授就此问题进行了专题报告。会后，《肿瘤瞭望》有幸采访了Marks教授。

　　Oncology Frontier:With new novel agents becoming available， what is your treatment of choice in aged patients with ALL?

　　《肿瘤瞭望》：请问目前是否有在初治和复发情况下都可以应用的临床新药？

 

　　Dr Marks: Older patients tolerate more aggressive chemotherapy less well， particularly in the relapsed setting. We have standard regimens such as FLAG or FLAG-IDA which may be unduly toxic. So there is a lot of interest in looking at the new immunotherapeutic agents such as blinatumomab and inotuzumab. Very shortly， there will be results from the inotuzumab phase III study randomizing inotuzumab against standard of care. Pfizer have released some details showing the complete remission rate with inotuzumab is superior to other standard of care chemotherapy， but we need to see if it improves survival. With blinatumomab， there is a randomized phase III study called TOWER that is recruiting extremely well. It will probably close ahead of recruitment targets， but we will have to wait maybe eighteen months to get results. Nonetheless， that drug has been licensed by the FDA in the United States， but for it to come into use globally， we will need the phase III data.

　　Marks教授：老年患者对高强度化疗的耐受能力较差，尤其是复发患者。一些标准化疗方案如FLAG 或FLAG-IDA，因为这些方案毒性较大，老年患者多不耐受，所以迫切希望新的免疫治疗药物如blinatumomab和奥英妥珠单抗（inotuzumab）可以发挥其最佳治疗作用。一项奥英妥珠单抗的III期随机研究比较了奥英妥珠单抗与标准治疗，其结果将很快公布。不过，根据辉瑞的一些报告显示，奥英妥珠单抗的完全缓解率优于标准化疗，但还需要看是否能改善生存。关于blinatumomab的随机III期试验目前刚刚完成招募，最终研究结果要等18个月后才能见分晓。虽然blinatumomab已获得美国FDA批准，但若要在全球应用仍需有III期试验数据的支持。

 

　　Oncology Frontier: What’s the role of tyrosine kinase inhibitors?

　　《肿瘤瞭望》：酪氨酸激酶抑制剂、靶向抗体和免疫性T细胞在CLL的治疗地位？

 

　　Dr Marks: That’s an essential part of the regimen for older patients if they have Philadelphia-positive ALL. There is no data that there is anything better than imatinib and that should be the starting drug. If patients relapse， it is worth trying different TKIs， dasatinib and perhaps erlotinib. Dasatinib has some data in induction， but has never been shown to be superior to imatinib. It is a different drug; it inhibits Src. It also penetrates the blood-brain barrier， so for patients with CNS disease， it may be the drug of choice. But it also has some toxicities.

　　Marks教授：对Ph(+)ALL老年患者来说，酪氨酸激酶抑制剂是治疗方案的必备要素。尚无数据表明其他药物优于伊马替尼，所以伊马替尼应当在治疗开始就应用。如果复发，有必要试用其他TKIs，如达沙替尼或厄洛替尼。现在有一些关于达沙替尼用于诱导治疗的数据，但未显示它优于伊马替尼。达沙替尼的作用机制是抑制Src，还能穿透血脑屏障，所以对有CNS侵犯时采用达沙替尼治疗可能更优，当然它也有一些毒性。

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