Nigel Russell教授分享急性髓系白血病国际最新治疗进展

一年一度的欧洲血液学协会年会（EHA）于近日在德国法兰克福以线上线下相结合的形式顺利举行。作为欧洲血液学领域规模最大的国际会议，每年都有来自全球100多个国家的10000余名专业人士与会，一起分享并探讨有关血液学的创新理念及最新的科学和临床研究成果。本次大会虽已结束，但会上专家学者们分享的精彩内容仍令人回味无穷。《肿瘤瞭望》特别邀请到英国伦敦盖伊和圣托马斯NHS（英国国家医疗服务体系）信托基金会Nigel Russell教授，就本次大会上有关急性髓系白血病（AML）的最新治疗进展及相关研究进行分享。

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《肿瘤瞭望》：FLT3抑制剂联合强化化疗是FLT3突变AML的治疗选择之一。能否请您谈谈在EHA大会上这方面有哪些进展？

Nigel Russell教授：近年来，Midostaurin联合强化化疗一直是FLT3突变AML的标准治疗方案。在本次会议上，我们介绍了强化化疗与Gemtuzumab Ozogamicin（GO）以及Midostaurin联合使用的数据。这些有力的数据表明，FLT3抑制剂联合强化化疗可延长患者的生存期，且GO具有安全性。我认为这是一个发展中的领域，欧洲的其他研究组也对使用这种联合疗法很感兴趣。此外，其他FLT3抑制剂也正在投入使用中，比如Quizartinib。最近有一些关于强化化疗与Quizartinib联合治疗FLT3突变AML的有趣数据呈现，因此有多线研究正在进行中。

Oncology Frontier: Our first question is a combination of FLT3 mutation inhibitor and intensive chemotherapy is one of the treatment options for FLT3 mutated AML. Could you please talk about the progress at this EHA congress?

Midostaurin has been a standard of care with intensive chemotherapy for a few years. We at this conference presented the data on the combination of intensive chemotherapy with gemtuzumab ozogamicin (GO) and with midostaurin. And we present some really effective data to show that the survival of these patients appears to be increased in the combination of a FLT3 inhibitor with chemotherapy, with gemtuzumab is possible and safe. I think this is a developing area and other groups in Europe are interested in using this combination. Otherwise, other FLT3 inhibitors are becoming on stream such as quizartinib. There's been some interesting data presented recently about the combination of intensive chemotherapy and quizartinib of FLT3 mutated AML so there's a number of lines of interests that are being developed.

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《肿瘤瞭望》：您的团队口头报告了一项关于使用FLAG-Ida方案与GO联合治疗NPM1突变AML的研究（摘要编号：S134）。能否请您分享该研究更多细节？

Nigel Russell教授：FLAG-Ida是一种非常常用的强化方案，用于治疗复发性AML。我们将其与GO联用，命名为FLAG-Ida-GO方案，并在一项大型研究中与柔红霉素（DA）3+7化疗加GO（DA-GO）进行了随机比较，并特别关注亚组的研究数据。研究共分析了300例患者，结果发现，在NPM1突变患者中，与DA-GO标准治疗相比，接受FLAG-Ida-GO联合治疗患者无事件生存（EFS）和总生存（OS）均显著改善，5年OS提高了18%。因此，对于这类患者而言，这是一个相当令人信服的获益。我认为这种联合治疗有望成为标准治疗方案。然而，与标准治疗相比，患者在FLAG-Ida（GO）治疗第二个疗程后血液学恢复有所延迟。

Oncology Frontier: An oral study reported by your team. The abstract 134 is for the combination of the FLAG-Ida regimen with GO to treat patient with NPM 1 mutated AML. Could you please share more details of it?

FLAG-Ida is a very commonly used intensive regimen for the treatment of relapse AML. We have combined it with gemtuzumab in a regimen called FLAG-Ida (GO) and randomized this in a large study against chemotherapy DA 3+7 plus GO and we're particularly focusing on subgroups There were 300 patients in the analysis. And we found the patients with NPM one mutations had a significantly improved event free and overall survival with the combination of FLAG-Ida (GO) comparing to the standard of care of DA GO. This resulted in an 18 % of improvement in overall survival at 5 years. So it's a fairly convincing benefit for this group of patients. I think this combination could become a standard of care. However, patients, particularly after the second course of therapy of FLAG-Ida (GO), do have delayed count recovery compared to standard treatment.

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《肿瘤瞭望》：能否请您简要介绍一下，双特异性抗体治疗AML的最新进展？

Nigel Russell教授：首先，双特异性抗体在AML中的发展并没有像在急性淋巴细胞白血病（ALL）中那样成熟。Blinatumomab是针对CD19的双特异性抗体。我们一直在用它治疗复发的核心结合因子AML患者。虽然在这里没有展示数据，但我们的治疗结果显示Blinatumomab的耐受性良好。在一些患者中，我们观察到了微小残留病（minimal residual disease，MRD）的根除。我认为采用双特异性抗体的靶向治疗将对MRD极为有效。AML患者在接受强化化疗后仍显示MRD阳性，使用类似一直用于ALL的双特异性抗体可以帮助根除MRD并治愈患者。

Oncology Frontier: Could you please briefly talk about the latest advancing bispecific antibodies in AML.

Bispecific antibodies have not really developed in AML in the same way that they have developed in ALL that's the first thing to say. We've been using blinatumomab, which is the bispecific antibody targeting CD19. We've been using that for patients with relapsed, core binding factor, leukemia. And we haven't presented the data here, but we treated a number of patients with blinatumomab, and it's been well tolerated. And in some patients, we've seen eradication of minimal residual disease, I think this kind of a targeted therapy using bispecific antibodies will be particularly useful in the setting of minimal residue disease. After patients have had intensive therapy, they remain MRD positive, and then use of bispecific antibody as has been used in ALL could help eradicate MRD and cure patients.

Nigel Russell 教授

英国伦敦盖伊和圣托马斯NHS（英国国家医疗服务体系）信托基金会