Hypomethylating agent for newly diagnosed TP53-mutant AML | Talher Badar, MBBS, MD

Hi everyone, I am Talhabadur Hematologist at Mayo Clinic and I will take this platform to discuss our study in which we evaluated the outcomes of very high risk unfavorable acute monorechemia and response to therapy. So what we know about this disease that P3 mutated AML tends to have a very poor outcome and conventional chemotherapy approaches haven't done well with modest response rate and survival outcomes. Most of the times these patients are elderly who may not be able to tolerate more intensive chemotherapy regimens. So usually less intensive chemotherapy approaches such as hypoptenic agent, we call them decitabine or azacytidine are applied to improve outcome. And having said that, their outcomes compare to intensive chemotherapy approaches. And there are some earlier studies that suggest that one form of hypoptenic agent therapy such as decitabine may work better for this disease. However, to our anecdotal experience and reading through various trials, we would like to evaluate if it's the case in a larger group of patients who are studied across 15 academic centers across the United States and to have a real poor perspective. So among the group of 350 patients with this high risk disease, we saw we did a match control analysis to see if decitabine is really the winner when it comes to outcome in comparison to a sister drug called azacytidine in management of P3 mutated AML. Our analysis suggests that the baseline characteristics that are determinant of outcome such as chromosomal type such as white cell count, such as complex cytogenetics and all these factors tends to affect how these patients do, they are comparably matched between the two groups. We figured it out that decitabine has ensured to have a better outcome compared to azacytidine in a matched group population. However, patients who achieve remission and those who were successfully bridged to bone nerve transplant tends to have a survival advantage. Venetoclax is another therapy that has been implied in combination with decitabine or azacytidine to manage these patients. In our analysis, we suggest that venetoclax based combination didn't improve outcome, but may lead to increased toxicity in elderly AML patients who are ineligible to receive intensive chemotherapy approaches. So in conclusion, I would suggest that decitabine and azacytidine had comparable outcomes. Decitabine is available in oral formulations, so maybe more convenient to administer in a really patient population preserving their quality of life and less with this to the hospital. However, if we can successfully bridge eligible patients to bone nerve transplant, we can improve their outcome from less than six months to median around 30 to 40 percent of patients who can have a survival more than two years and more. So that is the bottom line of our study. Thank you. If our videos have helped you in any way and you are able to, please consider making a donation to help us continue this important work. Your gift will go three times as far when we reach $500,000 by the end of the year. Every contribution, big or small, makes a difference, and we're deeply grateful for your support. Thank you.