一年一度的欧洲血液学协会年会（EHA）已于当地时间2023年6月8～11日在德国法兰克福以线上线下结合形式顺利举行。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多个国家的万余名专业人士与会，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。在本次EHA上，哈佛医学院（HMS）Amir Fathi教授口头报告了一项目题为“menin抑制剂Ziftomenib在成人复发/难治性NPM1突变急性髓系白血病（AML）患者中的活性、耐受性和耐药性”的研究。《肿瘤瞭望》特别邀请到Amir Fathi教授，就该研究及AML靶向治疗相关进展进行解读。

Amir Fathi教授：NPM1突变通常与一线治疗中良好的预后有关。但我们在演讲中也提到，若患者年龄较大、存在其他共存突变（concurrent mutations）以及复发难治情况下，携带NPM1突变的患者的预后差，表现出较差的疗效。因此，我们迫切需要针对NPM1突变的靶向治疗来应对这种高度未满足的临床需求（high unmet need），以改善这类患者的预后。

 

Oncology Frontier：Could you please discuss the impact of NPM one mutation on the prognosis of acute myeloid leukemia(AML)patient?And what is the values of the treatment?

 

NPM one mutations are historically associated with a favorable prognosis in the frontline setting，but our nuances to that，as I mentioned in the presentation，if patients are older，if there are certain concurrent mutations，and in the relapse refractory setting，patients with NPM one mutations do not do as well and actually do quite poorly.Therefore，I think there is a high unmet need for NPM one targeted therapy to help improve the outcome of these patients.

 

Amir Fathi教授：Ziftomenib是一种强效的menin-KMT2A相互作用抑制剂，通过下调特定调控因子，例如HOX19和MEIS1，促使髓系原始细胞(myeloid blasts)分化为正常髓系前体细胞（myeloid precursors），从而达到临床疗效。

 

在这项Ib期研究中，我们重点关注携带NPM1突变的复发难治患者。我们发现该治疗方案在患者中耐受良好，客观缓解率（ORR）为45％，完全缓解（CR）率为35％。更多的分析仍在进行中，并且目前正在进行II期研究。随着时间的推移，我们将会有更多的了解。

 

表1对Ziftomenib治疗的反应

 

Oncology Frontier：Could you please introduce more details of your LB2713 study?

 

Ziftomenib，as a potent inhibitor of the menin-KMT2A interaction on histones，down regulates certain regulators，specifically HOX19 and MEIS1，leading to differentiation of myeloid blasts into normal myeloid precursors and ultimately a clinical response.

 

In this phase Ib study，we focus our attention during this presentation on NPM one mutated patients.We found that the treatment was well tolerated in relapse refractory patients，and led to an overall response rate of 45%and a complete remission rate of 35%.Analysis is ongoing，and a phase two study is currently underway.We will find out more over time.

 

Amir Fathi教授：我认为目前AML的治疗方案仍在不断发展。menin抑制剂类别的药物非常有潜力。CD47/SIRPα的靶向药物也很有趣。本次大会上有一些关于menin抑制剂耐药性的最新报告非常引人注目。因此，本次大会十分重要，我们也在此次大会和其他的全球性会议上得知一些最新的进展。

 

Oncology Frontier：Could you please talk about other developments advances in targeted therapy in this conference?Do you have any study that made you the most impressive?

 

I think the current landscape of AML probably continues to evolve in terms of therapies.The menin inhibitor classes are intriguing.The CD47/SIRPαtargeting agents are intriguing.I think there was also some recent presentation on resistance to menin inhibitors at this congress that I found to be very interesting and intriguing.So I think it was a good congress，and we’ve had some very recent developments at this congress and also other meetings globally.

 

Amir Fathi教授

哈佛医学院（HMS）医学部，擅长急性髓系白血病（AML）、白血病、骨髓增生异常综合征、血液系统疾病、慢性髓细胞性白血病（CML）等。