DR CORTES: Some people say, for example, for the FLT3 inhibitors, they say, “It’s unfortunate it’s not like imatinib.” And it is exactly like imatinib. What’s not like imatinib is the disease. If you look at imatinib in blast-phase CML, it does exactly the same. It brings the blasts down. It gets a little bit of a remission, and then they come back. It’s a very molecular heterogeneous disease, AML, so a single-agent therapy is unlikely to work.

So then we focus on it’s a dirty drug, and we want a very specific drug. It depends on how much of the dirtiness is useful or not and how much of the specificity could affect other cells that may be valuable. And the other thing that we have is, if you’re going to kill cells that are not leukemic, are they dispensable or not? With monoclonal antibodies, for example, the B-cell monoclonal antibodies, we eliminate all the B-cells. It’s not like CD19 or CD20 are specific for the leukemia. They’re specific for B-cells, but if you can get rid of the B-cells, you can be okay. But if the target is expressed in other cells, are you going to be okay?

So a lot of these, we’re trying to understand. There are very few — mutated proteins are probably better examples. And in that regard, for example, IDH is perhaps the best example of something that’s very unique to the leukemic cells. It works very differently, and the inhibitors only affect the mutated IDH, not the nonmutated IDH. But other than that, if you’re inhibiting FLT3, the mutated and the nonmutated, but the normal hematopoetic cells need FLT3.

So we are starting to understand how much dirtiness, how much specificity, how much — what exactly do we need? And I’ll just end by emphasizing that single-agent therapy in AML, it’s very unlikely to get us a significant number of cures.

Module 1: Current and future approaches to targeted therapy for acute myeloid leukemia (AML)

Module 2: Other clinical issues in AML management

Module 3: Case discussions