ASCO 2025 | Key factors that influence conditioning intensity and moving toward personalized conditioning in AML

So generally, patients are given an intense conditioning regimen. The principle is if they can tolerate it. We would like to give an intense conditioning regimen to everyone because we know that that reduces relapse rate, but this is at the expense of non-relapse mortality. So generally, most centers would have an age cutoff somewhere between 60 and 65, over which they would give reduced-intensity conditioning. The other factor that they would consider is patient comorbidities. So patients with higher comorbidity are at higher risk of non-relapse mortality, and obviously that is a consideration. So even younger patients, sometimes with high comorbidity, one would choose a lower-intensity regimen. 

So I think in transplant, we are somewhat behind induction therapy and other therapies, induction and salvage therapy, for this disease. But that said, we have several things we are doing towards this personalized goal. So one of the first things many years ago we did was to give a personalized dose of myeloablative busulfan. So we would give a fixed dose of busulfan, as we did in this trial itself, 80 milligrams per meter squared, and then you measure the drug level, and you adjust the subsequent doses based on pharmacokinetic analysis. So if you will, you are giving the personalized dosing of the drug, in this case, busulfan, based on how the patient eliminates the drug. Something similar has been done with other agents also. 

So the second part, which is shown in this particular study, is now that we have targeted agents available, would we combine them with our conditioning regimen? And would that improve outcome or reduce relapse rate? And in this study, one of the important principles we demonstrate is that yes, you could give sorafenib. Now, one of the nice things about the way our regimen is, is that it is given over a three-week period, so you could give sorafenib over a three-week period along with chemotherapy to enhance the synergy. So one nice advantage of this long regimen is that it allows us to add agents. So sorafenib is one. 

We have also another study where we have added venetoclax to this long backbone regimen, and again, shown good results. And I think this is one of the ways we can incorporate targeted therapy in our patients. Also, there are a lot of efforts underway to use this in a maintenance setting, just like what we do with, say, induction therapy. So many of these agents are used in a maintenance setting. So a lot is done, but a lot more needs to be done.

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