ASH 2024 | The BLAST AML-2 trial: the addition of pembrolizumab to azacitidine and venetoclax in AML

This was another abstract that was presented by one of our outstanding fellows at the O’Neal Cancer Center, Dr Jessica Stemple, who helped describe the final analysis from what we colloquially call the BLAST2 trial, also known as NCI10334, which is a randomized trial comparing a reference standard of care, azacitidine venetoclax, to a triple regimen, including the PD-1 inhibitor pembrolizumab, which has a number of indications in pretty much all solid tumors, I would say. This is based on preclinical evidence that leukemic blasts overexpress a ligand, which can be impacted in a good way to hopefully treat these cells. And we thought we could induce greater depths of remission. The primary endpoint of this trial was MRD negative complete remission, MRD negativity as assessed by flow cytometric analysis, and more specifically, centrally assessed with a trusted colleague by the name of Brent Wood at Cincinnati, or actually now at LA Children’s Hospital. After a fair amount of follow-up, this trial was terminated prematurely by a DSMB decision after we had enrolled about 60 patients, and comparing these patients, AZA-VEN versus the investigational triplet, We found that there was actually no difference in the rates of MRD-CR or other means of measuring effect at least in less intensively treated patients with AML. I would offer that we did find what appeared to be an imbalance in disease risk, but more so the predicted benefit of getting azacitidine venetoclax, which we now have more of a novel system to actually qualify if patients have a predicted likelihood of benefit, intermediate likelihood of benefit, or low probability of benefit. There was an imbalance, unfortunately, trending towards the investigational arm to having more enrichment for patients who had less likely benefit to the backbone AZA-VAN. And this did translate to no improvement in survival. In fact, a trend towards worse survival, and the same goes for progression-free survival. So even though this trial was negative, we hope that this, to my understanding, the only randomized trial in AML using a PD-like immune checkpoint inhibitor, a classical immune checkpoint inhibitor will inform the next generation trials. We have a number of correlative analyses that are underway and otherwise being planned so we hope that this can at least be the saving grace for what is an important albeit negative trial.

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