ISAL 2023 | Standard treatment of elderly patients with AML & evaluating IDH inhibitors in younger patients
Alan Burnett, MD, University of Glasgow, Glasgow, UK, comments on the standard treatment of elderly and frail patients with acute myeloid leukemia (AML), highlighting some of the challenges in evaluating IDH inhibitors in clinical trials in younger patients with AML. According to Dr Burnett, it is important to determine the optimal dosing schedule for the combination of azacitidine and venetoclax instead of investigating triplet therapies that may lead to higher toxicity. Moving foward, Dr Burnett notes that while IDH inhibitors have demonstrated efficacy in elderly patients, evaluating their efficacy in younger patients poses a challenge due to difficulty in recruiting large numbers of patients for clinical trials. This interview took place at the 18th International Symposium on Acute Leukemias (ISAL XVIII), held in Munich, Germany.
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Transcript (edited for clarity)
Well, this is the population that, you know, for many years was ignored. We opened a study in the UK quite a long time ago giving the patients low dose ara-c and that produced a few remissions, 15%. And if they got a mission, they had, you know, several months of remission. Azacitidine was introduced and to my mind it was always a bit controversial how much better than low dose ara-c it actually was...
Well, this is the population that, you know, for many years was ignored. We opened a study in the UK quite a long time ago giving the patients low dose ara-c and that produced a few remissions, 15%. And if they got a mission, they had, you know, several months of remission. Azacitidine was introduced and to my mind it was always a bit controversial how much better than low dose ara-c it actually was. But anyway, people voted with their feet and adopted azacitidine. The disadvantage is that it had to be given prudentially. More recently, oral azacitidine has become available, but it was a bit difficult to do the study at the beginning, but that’s helpful for older patients. And then you’ve got venetoclax adding considerably to that benefit. And then you’ve got the other stuff which is new, which you’ve got a triplet. Now sometimes when you add them together, they’ll get more toxicity or myelosuppression than you would want. So I think the challenge at the moment, rather than doing randomized trials to see if they’re better is just to make sure the combination and the dose scheduling is correct and there’s a lot of activity going on with that. And so that’s that. And then the other thing that has been known about for a while is that if you have some mutations of IDH1/2, there are now potential inhibitors and if you use them in combination either with low dose ara-c or with azacitidine, that’s pretty helpful. The real challenge now is how do you show in the young patients with these mutations? And I think there may be about 12% of patients will have these mutations to get enough numbers to do a trial on them. And this is a challenge for the HOVON and collaborating groups where they think they need 7000 new patients before they find enough to do the randomized study of the of the addition of the IDH1/2 inhibitors. But that study has been done. I may be mistaken but I think the readout of that was stated to be 2033. So I may be wrong in that, but it may be a misprint in something I read. So there’s a lot of challenges now that for, for collaborative groups wanting to do clinical studies and they’re difficult to do. The numbers are probably more difficult to get hold of, but you’ve still got to satisfy the regulators.
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