ASH 2025 | Predicting and preventing therapy-related myeloid neoplasms

We talked about our ongoing study at Weill Cornell in the scientific session at ASH 2025. We wanted to, you know, as we understand that somatic mutations do precede myeloid malignancies, the place where this is actually most relevant is in therapy-related myeloid neoplasms because, you know, these are devastating diseases. If there’s a way for us to predict these diseases early and do somewhat of an intervention to prevent therapy-related myeloid, this is a huge, huge thing we can do for our patients undergoing chemotherapy or radiation. So we took, this was a work that was funded by the Department of Defense, where we took patients with prostate cancer who are getting PSMA-targeted radiation therapy. And what we’re able to do over many years is take samples before the treatment and then follow serially. And there were a few things that we found. And, you know, the whole premise of this is to identify who should be screened for these pre-malignant mutations, how to track them, and how do you do outcome management. Because in the end, you have to stabilize the clones and at the same time help them get through their prostate cancer therapy. You can’t stop one or the other. So there were some key takeaways that we found. The first thing is these pre-malignant somatic mutations are present pretty commonly in this population. Almost 46% had these mutations. But of them, about 10% were the high-risk clones that were worrisome for therapy-related myeloid disorders in the future. So there is a way to screen these people. We know they exist, but how do you know who to screen? So the couple things we proved is that if these patients, when they’re getting these targeted radiation therapies, if they get profound anemia after the first cycle, just anemia, not other cytopenias, those are the people who have a high risk for having these pre-malignant mutations. So that’s the time to screen. And if at the end of the therapy, that was another time point, if they had worse anemia from where they started off, that is another place where these patients were more likely to have the mutation. So these are the two time points we’re telling our solid tumor oncologist. This is when you have to refer the patient to the hematologist or work this up. And if you find these high-risk TP53, PPM1D, and complex clones, then we’re tracking them. And what would be ideal is to give these therapies, and what we are doing at Cornell is we’re trying to enroll them into our clinical trials for monitoring and early intervention so we can stabilize the clones and at the same time sort of give intermittent therapy for prostate cancer. So you’re trying to do both, control prostate cancer and control the clone. So these are very interesting data that gives real evidence and guidance to how these patients can be pulled through both conditions in a reasonable way.

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