Harry Erba, MD, PhD: Dan, I want to pull you into the discussion a little earlier than we had planned. Talk to us about some of your considerations about how you pick the right therapy. I know you’ve made some comments about whether fitness is important anymore.

Dan Pollyea, MD, MS: In the environment in which I was trained—and up until just a few years ago, for all of us—the most important initial consideration was if the patient was a candidate for intensive induction chemotherapy. If they were, that’s what you did. If they weren’t, you didn’t do a whole lot that could help them. We have data to show that over half of AML [acute myeloid leukemia] patients didn’t get treatment. Some of us were negative about learning about that data, but when you see the reality of the poor options and the horrible outcomes on the ground, it’s not surprising that people were so nihilistic.

In the last 3 years in which we have practiced, things are completely different. The assessment of the fitness for intensive induction chemotherapy may need to be updated in an era when we have other treatment options. A patient’s ability to withstand or not die from intensive induction chemotherapy in the modern era doesn’t necessarily commit them to that treatment. Mark was getting at this with his need for an early look at TP53.

You can be fit for induction physically and may not die from that treatment, but the question is whether your disease will respond to that treatment. If there’s a patient who is unlikely to die who also has disease very unlikely to respond to it, then the way I’d like to see things move is not to suggest that treatment for that patient. What I hope is happening is that the definitions or the assessments of fitness for induction will start to melt away. What I hope will happen instead is we’ll have a new standard for which you have to prove yourself likely to respond to induction chemotherapy to be a candidate for induction.

For people who have a curative option from intensive induction chemotherapy, that’s a very reasonable standard. For core binding factor or other patients with certain molecular signatures, other people who historically may have been fit for intensive induction chemotherapy, I don’t think that that’s appropriate for them anymore in the modern era. We’re going to talk at length in this panel about some of these other exciting therapies, so things are changing.

Mark Levis, MD, PhD: We should not focus so much on intensive therapy but on effective therapy. You can take an unfit patient and make them fit with effective therapy. You can take a fit patient and make them unfit with ineffective therapy.

Dan Pollyea, MD, MS: That’s exactly right.

Naval Daver, MD: I agree very much with Dan. The question that we all had in training was about who is absolutely not fit to get induction, and we’re going to use that as exclusion and then give it to others. A lot of data [have] come out, studies are being done, and phase III data [have] to be reviewed, but the hope is that now it will hopefully switch in the next few years. We can ask, “Who really needs induction? Can we not give induction to people who can get something that’s equal or better and then leave them out.” It’s the inclusion-exclusion switch, which is—at least in the US [United States]—the hope for the further drive is moving.

Harry Erba, MD, PhD: I agree with these comments, but it’s made it even more complicated because no one agreed on what fitness meant in the first place, and now we’re adding in appropriateness for intensive chemotherapy, so where do you draw the line? Core binding factors, very curable. Adverse karyotypes [and] TP53, not curable with intensive chemotherapy. How about that large group of patients with intermediate-risk disease who have various risk factors? All this makes the decision making even more complex, but what we’ve learned is that we have time to slow down, put the brakes on, and think about what the best option is and what the goal of our therapy is for the next patient we see with AML.

Transcript Edited for Clarity