ASH 2024 | Assessing purine-analog-based intensive chemotherapy combined with venetoclax for ND and R/R AML

Yeah, so this was a nice collaboration between our center as well as the team at Northwestern University, Dr Yasmin Abaza being the kind of one of the individuals there that spearheaded the charge from their end. So as a fellow working under Dr Courtney DiNardo at MD Anderson and Dr Tapan Kadia, we utilized a lot of purine-based intensive chemotherapy regimens incorporating venetoclax for younger and fitter patients for frontline therapy for treatment of their AML. So these are regimens such as CLIA with venetoclax or FLAG-IDA with venetoclax. And by and large, that has predominantly been used within MD Anderson and has not been broadly adopted across the United States, and so this is a regimen that I use commonly at OHSU having trained at MD Anderson and feel comfortable with it and same with Dr Abaza at Northwestern. And so what we really wanted to do with this pooled analysis was to say, hey, how do our outcomes compare to those that have been observed at MD Anderson? Can we replicate those results? And do we still see improved response rates and prolonged survival when we incorporate venetoclax with these intensive purine analog-based induction regimens? 

So this was a retrospective study between the two sites. It included newly diagnosed AML patients as well as relapsed/refractory AML patients. The cohorts were separated for the analysis. 

And what we observed was that in the newly diagnosed AML population, the incorporation of venetoclax with intensive chemotherapy indeed resulted in high composite CR rates in the range of 90 to 95% for patients across ELN risk groups, and this translated into favorable overall survival. We then compared this patient population to the BEAT AML cohort, which is a cohort of patients that received intensive chemotherapy, or rather I should say we limited the analysis to those patients that received intensive chemotherapy, but without venetoclax. And in this patient population, we saw that intensive chemotherapy combined with venetoclax had improved overall survival after adjusting for things like transplant and ELN 2022 risk group compared to standard intensive induction chemotherapy. 

In the relapsed/refractory AML population, we also saw some important findings that previously had not been discovered or not really been able to be evaluated is a better way to put that. And what I mean by that is we first replicated the results that were observed in the initial Phase I, Phase II studies. We saw composite CR rates in the 60 to 70% in a relapsed/refractory AML patient population and a median overall survival that extended beyond a year. 

Now what was interesting was, this was also true in the frontline cohort, is we did exploratory analyses looking at the impact of TP53 mutations. This is a molecular subgroup that’s known to be resistant to venetoclax-based therapy. And in both the frontline and the relapsed/refractory cohorts, patients with TP53 mutations had inferior overall survival. Similarly, in the relapsed/refractory cohort, patients that had received prior venetoclax as part of a lower intensity therapy regimen and then received intensive chemotherapy with venetoclax following that had inferior overall survival. And so we were able to help refine, okay, who are these patients that have relapsed/refractory AML who may most benefit from this regimen. Those would be patients without TP53 mutations and who have never received prior venetoclax and those patients had favorable survival outcomes even despite the fact of having relapsed/refractory AML.

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