Individualized Approach to Treating AML Patients | Pamela Becker, MD, PhD | ASH 2022

I'm Dr. Pamela Becker from City of Hope in Dorcha, California, and I will be telling you about a presentation that was set at American Psych for Hematology on December 11, 2022. I presented work on a clinical trial that was enrolled patients with acute myeloid leukemia, and it was a precision medicine trial in that each patient had their cells tested in a laboratory test against 170 drugs and drug combinations, and then we chose what the best drugs were for the patient. In addition, we tested for mutations and added the small molecule inhibitors that were appropriate for patients with those mutations. So we presented the long-term follow-up data, which included overall survival, and for the patients who were able to receive the drugs and drug combinations that we recommended, there was improved survival compared to those that had to go home or didn't get insurance authorization or whose doctors decided to choose other therapy, including other clinical trials and CAR T-cell trials and other options. And so it was very exciting to finally see these data, and this was true not only for all patients enrolled on study, but also for the patients who had relapsed early after allogeneic transplant. The patients who relapse after allogeneic transplant often are quite poor risk. They have very aggressive disease, and even for those patients, they were able to exhibit prolonged survival. So it was very exciting to be able to present those data. The session was a session that was on the latest developments that were technological developments, and so I was also able during this trial to procure specimens from the patients. We were able to correlate gene expression with drug sensitivity or resistance, and this will be very helpful for the future. This was a machine learning algorithm. Machine learning is part of artificial intelligence, and so we're able now to use that information in a future clinical trial where we would choose drugs for patients. And we also were able to develop another model, which is the co-occurring mutations. So patients who have blood malignancies exhibit usually more than one mutation, usually dozens of mutations, up to dozens of mutations. And in order to best take those different mutations into account in terms of choosing treatment, we established a model with my colleagues at the Institute for Systems Biology wherein we can look at the patient's network of mutations and correlate those with the drug sensitivity or resistance. This is another way that we'll be able to assign treatment in the future for these precision medicine approaches. Lastly, we looked at the single cell mutation panels to try to identify what clones are present. For all of the blood cancers, it's known that there is representation of many different clones. There's not just one people. We think of it as, oh, we have your cancer cell, but there's actually a group of cancer cells for all the patients, and they vary from each other. And so I was able to identify how many clones and what the relative composition is. And again, that will be something that we'll be able to utilize in the future to make sure that as we apply these precision medicine approaches that we are taking into account all the differences not only between patients, but even amongst the cells that make up the leukemia. So again, this is a first demonstration kind of of improved survival with a functional precision medicine approach. So we show a beautiful heat map that shows that every single patient, if you plot their results for all the drugs, 170 drugs, every single patient looks different from every other patient. So the question is, why are we ever giving the same drugs to all patients? So anyway, it was really gratifying to be able to present those data yesterday.