Therapeutic Approach for IDH2-Mutated AML - Episode 2
Courtney D. DiNardo, MD, MSCE:The most important part of the diagnostic workup is making sure you have the correct diagnosis. So, making sure that it truly is an acute myeloid leukemia. And then once you have that hematopathologic diagnosis, the cytogenetics and molecular features are really critical in determining what the appropriate therapy should be. And so, cytogenetics are fairly standard. We’ve been doing them for over a decade now, classifying patients into favorable risk or immediate and unfavorable. And then, more and more, the molecular annotation becoming part of our classification system.
I think every patient should have molecular testing performed. First of all, at their diagnosis. And that includes the 3 most standard molecular mutations:FLT3,MPM1, andCEBP-alpha, as well asP53. Those are part of the initial classification systems and prognostication. ButIDHmutations, now that there are targeted therapies available for patients withIDH1- orIDH2-mutated AML, that really needs to be part of the upfront diagnostic analysis of your patient.
In terms of when you should be doing additional molecular testing outside of diagnosis, I feel that it is helpful in patients who are in remission to repeat that testing to see if they’ve been able to obtain what we call molecular remission, or molecular MRD. And as well as in the future that patient relapses, or there’s a treatment change, molecular testing at that point is indicated because it can change. There are different clones that can evolve and so the relapsed leukemia you’re treating isn’t always the same as the leukemia that they had at diagnosis. And so, you always want to make sure you have informative information to make sure you’ve got the right treatment for your patient.
Most molecular testing done is part of a NGS panel, and that’s because now there are a half a dozen or more genes that are important in AML. And so, the cost of doing each one separately with standard sequencing is no longer the most cost-effective or feasible. Most institutions do it differently, laboratories do it differently, but in general, there’s a core panel of at least 6 to 8 mutations that are done. So, I do think panel testing is, more and more, the way to go.
Transcript edited for clarity.
Case: A 65-Year-Old Woman withIDH2-Mutated AML