ASCO18专访│CAR-T细胞免疫疗法有望改写多发性骨髓瘤标准治疗

作者:肿瘤瞭望   日期:2018/6/11 17:50:52  浏览量:24862

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编者按:第54届美国临床肿瘤学会(2018ASCO)年会期间,一项CAR-T细胞免疫治疗复发难治多发性骨髓瘤的多中心研究结果(摘要号:8007)引起了与会者们的热烈讨论。《肿瘤瞭望》记者现场邀请到参与此次讨论的Catherine M. Diefenbach教授,请她分享个人观点。Diefenbach教授是美国纽约大学Langone医学中心的血液学和肿瘤学专家,研究方向为淋巴瘤。

据Diefenbach教授介绍,此次ASCO年会发布的是bb2121抗BCMA CAR-T治疗复发、难治性多发性骨髓瘤的最新结果,是对2017年12月报道的Ⅰ期多中心研究数据的更新。
 
研究结果显示,在输注CAR-T细胞150×106的18例患者中,中位无进展生存期(PFS)为11.8个月,而目前大多数复发性骨髓瘤患者的平均PFS约为4个月,“所以这无疑是对现有标准疗法的一大改进。”
 
就CAR-T治疗反应时间而言,与白血病和淋巴瘤患者相比,多发性骨髓瘤患者的反应时间较短。Diefenbach教授认为,虽然CAR-T疗法相对于现有治疗存在实质性的改进,但仍有部分患者会随着时间的推移而复发,所以CAR-T治疗的疗效持久性需要进一步验证。
 
“CAR-T治疗为多发性骨髓瘤患者带来希望”,Diefenbach教授在采访中指出。虽然处于早期阶段,但是相对于所有的标准治疗,应用CAR-T治疗的复发、难治性多发性骨髓瘤患者已有PFS改善和更高的应答率。然而问题并没有得到完全解决,我们仍然难以阻止这些患者的复发,所以还有很多工作要做,还要付诸更多努力。
 
“我认为无论发生什么突变,大数据都会给多发性骨髓瘤治疗带来一些帮助”。在多发性骨髓瘤中,我们还没有真正的针对突变的靶向药物。另外,目前尚不清楚哪些患者对免疫疗法的应答较好,为什么有些患者疗效持久,而有些患者很快就复发。大数据将有助于回答其中的一些问题。
 
 
 <Oncology Frontier>: Please introduce the main point of bb2121 anti-BCMA CAR T-cell therapy in patient with relapsed/refractory multiple myeloma.
 
Prof. Diefenbach: What was presented here at ASCO 2018 was an update of data that was presented earlier in December last year in 18 multiple myeloma patients who were relapsed and refractory and heavily pretreated, and who were treated with this CAR T-cell product. The updated progression-free survival data is approximately 11 months, which is at the low end of the projected estimate for PFS for these patients. To put this into context, the average PFS for most multiple myeloma patients who have relapsed with current therapies is approximately four months, so this is certainly an improvement on standard therapy. However, compared to the response duration we see with CAR T-cells in leukemia and lymphoma with the products that are currently approved, this is of a shorter duration. It looks like more patients are relapsing over time. This does raise questions about the durability of this approach, although it still seems a substantial improvement over current therapy.
 
<Oncology Frontier>: What’s the take home message?
 
Prof. Diefenbach: The take home message is that CAR T-cells show promise in multiple myeloma. It is still early days, but we see improvements in PFS and a higher response rate with the use of CAR T-cells for patients who are relapsed and refractory to all standard therapies. However, it does not look like the problem has been completely solved as these patients are continuing to relapse. More work needs to be done.
 
<Oncology Frontier>: As Dr. Johnson mentioned, the CancerlinQ will work based on big data background, and in terms of immunotherapy for these patient, how would big data help them?
 
Prof. Diefenbach: I think big data will be helpful wherever there are mutations that are driving cancer. In multiple myeloma, we don’t really have drugs that target actionable mutations yet. In fact, when they looked at the target for these CAR T-cells, the BCMA, it didn’t seem to matter whether that was high or low for patients to have a response, so I don’t think we have a good sense yet in myeloma why some patients respond better than others to immunotherapy, and why some have a response that is durable and why some relapse quickly. Certainly, big data will help us answer some of those questions. So will delving deeper into the immunobiology of multiple myeloma. Hopefully together, those tools will help to unlock the next generation of therapies for multiple myeloma patients.

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