EHA 2025 | Treating older or unfit patients with AML: the current standard and future directions

I think there is now plenty of data that the combination of hypomethylating agents plus venetoclax is very tolerable and effective in these older unfit patients. I think that is clearly the current standard. As I mentioned, with the introduction of an all-oral version of this, it may be making life a lot easier for these patients. Now, I am a strong believer that the initial induction should be carefully monitored. I actually believe that most patients should be hospitalized, although I believe that community oncologists may not adhere to this practice. But I think any AML patient, particularly patients who have other comorbidities, do need some degree of supervision during the first cycle of therapy that becomes much less closely watched in the subsequent cycles. I think the other debate will continue to be the number of days of venetoclax that’s needed for such regimens. The French study suggested maybe only seven days of venetoclax would be as good, although if we look at the subsets of AML patients, it does appear that patients with certain molecular features, such as those with NPM1 or IDH mutations, do benefit from more protracted dosing of venetoclax in the first and subsequent cycles. So I think, like everything else that is going on in AML therapy and cancer therapy in general, I think we have to use a personalized approach for each patient and design the regimen based on the patient’s features. So, for example, in patients who have TP53-mutated AML, I do believe that there is still a role for venetoclax, but it’s not as important as in other subsets. But I think the addition of venetoclax, even in TP53-mutated patients to azacitidine or decitabine does improve their response rate. So if there is a potential for an allogeneic stem cell transplant, I still do believe that there is a role for induction addition of venetoclax in such regimens. Another regimen that has been extensively used at MD Anderson and is now being used in other places is the cladribine, low-dose cytarabine plus venetoclax, which is also very effective in this population. Finally, I think we are beginning to develop triplet regimens, and this is being a very exciting development, in my opinion. Traditionally, in cancer therapy, we have believed that a combination of several agents is more effective in reducing the risk of resistance in cancer patients and in leukemia patients in particular. So, I think addition of agents to the backbone is necessary. However, we do have to do this very carefully because there is a potential for increased toxicity. And, of course, these regimens have to be well designed to try to avoid losing any benefit from the increased toxicity.

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