Optimizing Targeted and Genetic Therapeutic Strategies for Patients With R/R Acute Myeloid Leukemia
At the 2025 Great Debates (GD) in Hematologic Malignancies meeting in New York, New York, Aaron Goldberg, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, New York, discussed optimizing patient outcomes through targeted therapies and genetic profiling in the treatment of relapsed/refractory (R/R) acute myeloid leukemia (AML).
Transcript:
Thank you so much, my name is Aaron Goldberg from Memorial Sloan Kettering Cancer Center here in New York City. It's a pleasure.
I was here speaking today at Great Debates in Hematological Malignancies about relapsed and refractory acute myeloid leukemia. We talked today about how we are very fortunate that we have more and more targeted therapies available. The challenge in relapsed/refractory AML is really, how am I going to really help the patient have the best outcome possible?
What I talked today about first was thinking about what are my goals for the patient? Who is a patient, how old are they? Are they a candidate for allogeneic stem cell transplant? Then, do they have a specific targetable mutation?
We're able now to actually have a number of specific drugs that are now FDA approved that target specific molecular abnormalities that are present in relapse refractory. One thing I highlighted was the importance of profiling. Even if a patient didn't have a particular mutation at diagnosis, for example, they didn't have a FLT3 mutation very often, maybe about 20% of patients may then acquire a FLT3 mutation even after they've been exposed to prior therapy. It's important to reevaluate and I spoke about the importance of profiling, and then if they have a FLT3 mutation, the standard FDA approved therapy is gilteritinib, a FLT3 inhibitor that actually was superior even to chemotherapy for patients with that particular type of mutation.
We talked about IDH1 and IDH2 mutations. We talked about olutasidenib as an option for patients with IDH1 mutations. We talked about ivosidenib, we talked about enasidenib for IDH2 mutations, and we talked about this whole new class of drugs for patients with relapsed/relapse refractory AML with either KMT2 rearrangements, which is where the FDA approval is. These are called Menin inhibitors. Menin inhibitors are a whole new class of drugs that work to differentiate the leukemia cells to more mature cells. There's going to be more and more indications for them. For example, they're being explored even in patients with NPM1 mutations, which represent about 30% of acute myeloid leukemia. I spoke about all of that and talked about how although outcomes are improving, I think we have a long way to go still.
The future, I think, is in clinical trials. We spoke about combination therapies, trying to combine agents in biologically meaningful ways. Then we talked about some really provocative kind of new agents that may be coming out into clinical trials soon. I talked about a possible inhibitor of an enzyme called NAMPT, which is important for making NAD and maybe using that as a new targeted therapy for patients with chromosome7 abnormalities.
I also talked about some research done at Sloan Kettering with specific immunotherapy. Patients with splicing factor mutations actually have new really unique proteins on their cell surface of those leukemia cells. There's been work out of our Omar Abdel Hobbs lab showing that you can actually design T-cell receptor sequences to actually target those neo estrogens. That may be on the future bench, potentially a personalized immunotherapy for some of these patients.
I talked a little bit about the present and a bit about the future. I think the future really is bright in AML, with biologically relevant clinical trials.
Source:
Goldberg A. Navigating Relapsed/Refractory AML: Genetic Profiling, Targeted Therapies, and Optimized Outcomes. Presented at the Great Debates in Hematologic Malignancies meeting. June 28-29, New York, NY.
