Abstract: In this interview, Dr. Amir Fathi provides insights into the impact of NPM1 mutations on the prognosis of acute myeloid leukemia (AML) patients, emphasizing the evolving nuances based on age and concurrent mutations. He highlights the high unmet need for targeted therapies to improve outcomes, particularly for relapse-refractory patients with NPM1 mutations.
The interview delves into the LB2713 study, focusing on Ziftomenib, a potent menin-KMT2A interaction inhibitor. Dr. Fathi details its mechanism, demonstrating downregulation of key regulators and differentiation of myeloid blasts. The phase Ib study in NPM1-mutated patients showed promising results with a well-tolerated treatment, achieving an overall response rate of 45% and a complete remission rate of 35%. Ongoing analyses and a phase two study aim to provide further insights. Furthermore, Dr. Fathi reflects on other notable developments in targeted therapy presented at the conference, including menin inhibitor classes and CD47/SIRPα targeting agents. He mentions intriguing discussions on resistance to menin inhibitors, underscoring the dynamic landscape of AML therapies. The interview provides a comprehensive overview of the latest advancements in AML targeted therapy, contributing to the ongoing evolution of treatment strategies.
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?
Dr. Fathi: 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.
Oncology Frontier：Could you please introduce more details of your LB2713 study?
Dr. Fathi: 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.
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?
Dr. Fathi: I think the current landscape of AML probably continues to evolve in terms of therapies. The menin inhibitor classes are intriguing. The CD47/SIRPα targeting 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.
TAG: EHA 2023, Interview, Hematological Malignancy, AML
