ASH 2024 | Early MRD negativity measured by NGS-based assessment predicts excellent outcomes in Ph- B-ALL

So we’re presenting an abstract looking at NGS-based MRD assessment in patients with Philadelphia chromosome-negative B-cell ALL. So we know MRD is very prognostic in ALL and now we have even better tools than we did before. We have next-generation sequencing assays that are sensitive down to 10 to the minus 6 or one out of a million cells. And so the question is, how does this change our treatment approaches, our algorithms in terms of the need for transplant? 

So really the standard of care has been patients with high-risk disease, like based on high-risk cytogenetic or molecular features, these patients should be referred for allogeneic stem cell transplant. But the question is, do these high-risk patients who achieve deep MRD negativity still benefit from transplant? And so that was really the goal of this abstract. 

So we identified about 160 patients who were treated frontline with Philadelphia chromosome-negative B-cell ALL and underwent this deep NGS-based MRD assessment. We found that after about one cycle of treatment, usually basically with a hyper-CVAD-based approach, we see about 25 to 35 percent of patients will achieve deep NGS MRD negativity, and actually similar rates of deep MRD negativity between patients who have high-risk cytomolecular features and those who have more standard-risk disease. 

So what we found is that even for patients who have high-risk cytogenetic or molecular disease if they achieve very early deep NGS MRD negativity those patients have excellent outcomes, even without allogeneic transplant. 

Now, if they don’t achieve early MRD negativity, even if, like after one cycle, even if they achieve MRD negativity at a later time point, let’s say, 2 or 3 or 4 months later, that is not protective for relapse, and these patients still have poor outcomes. 

So essentially, our findings suggest that those patients with high-risk cytogenetic or molecular features who achieve early NGS MRD negativity can have excellent outcomes even without stem cell transplant. However, those patients with high-risk cytogenetic or molecular features who have either delayed MRD negativity or do not achieve MRD negativity benefit from stem cell transplant. 

So I think this abstract really helps with our treatment algorithms. And I think it’s changing our thought about who are patients who are appropriate for stem cell transplant and suggesting that even some high-risk patients based on cytogenetic or molecular features may be able to be spared the morbidity and potential mortality associated with transplant if they have a very chemosensitive disease and they achieve very early MRD negativity.

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