ASH 2024 | The outcomes of intensive treatment for patients with AML who have failed venetoclax-based therapy

This is, once again, another COMMAND consortium-derived analysis which attempted to answer a question which is quite relevant for a population in critical need. Post-venetoclax exposure and presumably failure is a situation that patients need better options. Nothing seems to work well, if at all, especially when you’re evaluating the targeted agents like FLT3 inhibitors, IDH inhibitors, we published on this topic in the past, but what about patients getting intensive therapy after being committed to a frontline, less intensive HMA venetoclax regimen, which are mostly patients that are not necessarily unfit but have poor disease biology like TP53, where our preference is to use a less intensive therapy. But of course, just the nature of this disease risk being not so good, either patients don’t respond or the responses are not durable enough to really derive significant benefit. Many of these patients will still have a goal of being cured, which in this situation is mostly going to be transplant. In this case, an allogeneic hematopoietic stem cell transplant. Intensive therapy has a bit of risk. It’s obviously intensive. Patients have a higher risk of infection and other complications which can lead to treatment-related mortality or death. But some patients are willing to accept this risk just to kind of get to transplant and really derive this, albeit small, rate of cure. It hasn’t really been answered. So we did pool. It was a relatively small number, but sufficient to at least, we think, inform our hypothesis. We got, I think, 22 patients with a variation in types of intensive therapies they received. I think the plurality of patients received CPX-351. And unfortunately, as we expected, the median overall survival was quite insufficient, I believe at around five months. But some patients did derive long-term benefit, and we do think based on the follow-up, we did have some patients who were cured. So again, a relatively small analysis, but a real-world analysis, multicenter. And even though the results were underwhelming, still shows that amongst patients that you can select to receive these therapies, some patients can still benefit. Retrospective, so certainly, you have to look through the lens of selection bias, but this is why this was done at AML Centers of Excellence. We think we’re somewhat decent at selecting these patients.

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