Role of Intensive Chemotherapy in Young, Fit Patients With AML


Centering focus on first-line treatment modalities, panelists highlight the ongoing role of intensive chemotherapy in the management of AML.


Jorge E. Cortes, MD: Let’s move on to treatment. We’re going to start by addressing frontline treatment. We started talking about this issue of fitness, but I’d like to ask Margie about how we address the therapy. We talked about this intensive chemotherapy, and I’ve always thought that 7+3 was like a wimpy treatment, but it’s been around since the 1970s. Is that still the standard for the standard-risk patient. Are there deviations in some settings that you prefer to use? Focusing on the chemotherapy itself, are there areas where you focus differently for these patients?

Margaret T. Kasner, MD: First, I agree about 7+3. I don’t know about wimpy, but I’d be happy to see it fade off in the distance as we better understand what we could be doing for our patients. In terms of fit patients, we’re still focusing on cytogenetic and molecular markers to push us forward into what we’re going to do. Favorable-risk cytogenetic patients—core-binding factor patients, for example—are still using the 7+3 backbone with the addition of gemtuzumab ozogamicin because there are good data to support that those patients can move forward in chemotherapy-only path toward cure. At our institution [Thomas Jefferson University], that’s our standard for fit patients with favorable-risk cytogenetic disease.

For the remainder of the patients, the question is what other markers might they have? For FLT3-mutated patients, we’re adding FLT3 inhibitors to their standard, 7+3. There’s only 1 approved combination, which is midostaurin plus that combination of chemotherapy. But we have an [expected] FDA approval date [April 23, 2023] for quizartinib in combination with 7+3; that’s coming soon. We have a trial that has ended accrual, and it’s going to be a bit until we know the answer. [This study] looked at gilteritinib vs midostaurin in this up-front 7+3 setting.

Then there’s a whole slew of FLT3 inhibitors plus other bases like Vyxeos [daunorubicin, cytarabine], which is the liposomal version, essentially of 7+3; the data for that is also coming. For that group of patients, we still have that intensive chemotherapy with the inhibitor. The patients we pulled out of using aggressive chemotherapy are TP53-mutated patients. Biology, in terms of fitness for the patient, isn’t something we’re considering in our institution because 7+3 isn’t valuable in that patient population.

Clinical trial is a top 3 choice if we can do it. If not, then there are some data with other combinations like FLAG-IDA [fludarabine, cytarabine, granulocyte colony-stimulating factor, idarubicin]–venetoclax, which might be better than 7+3 in that patient population. Intermediate-risk [patients] have almost disappeared now that we have a better understanding of molecular abnormalities. That’s the group that I probably would have said got 7+3 most. Now they’re pushed into the adverse and better-risk categories. I don’t know if other people on the panel have thoughts in addition to that.

Jorge E. Cortes, MD: That’s a great overview. Before I turn to the others—we’ll go through all the categories you described because they all have unique features on how we address the treatment—I want to get back to the core binding factors. You mentioned gemtuzumab. Do you do it routinely in all your patients? Do you include gemtuzumab in the treatment? Do you use it with 7+3? At the MRC [Medical Research Council], they use it with FLAG [fludarabine, cytarabine, granulocyte colony-stimulating factor], which is more intensive. What’s your consolidation on these patients? For these patients, we don’t typically transplant as an initial attempt for the cure. How do you consolidate these patients?

Margaret T. Kasner, MD: We’re using 7+3. One reason…for that combination was that there’s a practical issue with fludarabine shortage. In our institution, we’re keeping our fludarabine for transplant patients or for patients who we feel need to get things like FLAG-IDA [fludarabine, cytarabine, granulocyte colony-stimulating factor, idarubicin], as opposed to where we feel that we have an appropriate combination chemotherapy for these patients. From a practical issue, we have that. We consolidate with high-dose cytarabine and gemtuzumab, which is not the same as with the study, where they got it only for the first 2 cycles and then 4 cycles total of high-dose cytarabine. There are challenges with this. Even young and very healthy patients, in my experience, have higher infection rates and more issues with platelet recovery than when we don’t use it. But the outcomes are excellent. That’s what we’re standardly giving to our patients.

Transcript edited for clarity.

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