The 12th Annual Meeting of the Society for Hematologic Oncology (SOHO 2024) took place in Houston, USA, from September 4th to 7th, 2024, gathering top experts in the field of hematologic malignancies from around the world to exchange the latest research findings and discuss new therapeutic strategies. At the conference, Dr. Eunice Wang from the Roswell Park Comprehensive Cancer Center in the United States presented the latest developments in the research and development of Menin inhibitors. For this, 'Oncology Frontier - Hematology Frontier' specially interviewed Dr. Eunice Wang and provided a wonderful interpretation around this topic.

Oncology Frontier-Hematology Frontier：What are some of the latest research findings on Megnin inhibitors that you will share in your presentation?

Dr. Eunice Wang：At this year’s SOHO meeting, I share the latest updates on Menin inhibitors for the treatment of acute leukemia and potentially other hematologic malignancies. Our research right now has reached a critical point where it’s about to be translated, we hope into commercially available drugs.

One of the leading candidates for Menin inhibitor therapy is for USA regulatory approval and that is based on data with up to now four different Menin inhibitors showing clinical efficacy and clinical responses in patients with acute leukemia which have refractory and relapse to up to 3,4,5 lines of therapy.

Overall, I summarize the current progress demonstrated that among these four agents, most of which are still in early testing that there are clinical complete response rates and in the range of 20% to 30% and overall survival benefit in the range of 6 to 8 months in the absence of allogeneic stem cell transplantation.

This is the first targeted therapy for patients with a specific biological disease characterized by KMT2A (MLL) gene rearrangement or by an NPMl mutation. These particular subsets of leukemia make up 5 and 30% of newly diagnosed acute myeloid leukemia cases. So the impact of these inhibitors can be felt on a large proportion of newly diagnosed and refactory acute myeloid leukemia patients. Future research was also discussed and will include to the ongoing clinical trials where these Menin inhibitors with, however, relatively low response rates are now moving into the upfront therapy and the novel combinations.

Oncology Frontier-Hematology Frontier：How do you think Megnin inhibitors will change the treatment strategies for MDS patients?

Dr. Eunice Wang：MDS patients don’t have a high percentage of disease driven by KMT2A rearrangement or by NPM1 mutation. However, there is data in the laboratory that has identified other biological subsets would characterized by specific mutations that may also be positively impacted or inhibited by Menin inhibitors. And these include patients both with AML and MDS characterized by what we think are transcription factor needs driven tumors. These are potentially mutations such as SF3B1, NOTCH1, ASXL1, MYD88. And currently there are ongoing clinical trials investigating whether these  Menin inhibitors may also be of use and induced clinical responses in those particular rotational subsets. If those trials read out that there might be have activity, then it would be quite reasonable to propose future clinical trials, looking at patients with free of leukemia or MDS to see whether this could impact on particularly high risk MDS patients prior to their over transformation to AML.

So we will have to wait and see, but the fact that this could impact additional numbers of patients with both AML and MDS is actually very impaired.

Oncology Frontier-Hematology Frontier：What do you think is the potential of Megnin inhibitors in future research on the treatment of hematologic malignancies?

Dr. Eunice Wang：Menin  inhibitors apparently seem to have  great impact in acute leukemia is both acute myeloid leukemia, as well as acute lymphocytic leukemia characterized by KMT2A rearrangements. We are hopeful that again, if they are active in other mutation or biological subsets that the benefits of many mutations could also be seen, not only in myelodysplastic syndrome, potentially a myeloproliferative disease that may also be characterized, for example, by ASXL1.

There is ongoing research looking to see whether Menin inhibitor could also be of use in other hematological malignancies like lymphoma. And Menin inhibitors that’s being explored more broadly. There are potential implications because of the key role and as a scaffold protein to see whether there might even be solid tumor disease which could be affected by this. So this opens an entirely new field of investigation for us.