The Emerging Role of FLT3 Inhibitors in AML and ASM - Episode 2

AML: Induction Therapy and Minimal Residual Disease

Transcript:Richard M. Stone, MD: My approach to the patient with AML takes into account host and disease factors. Host and disease factors mean the patient’s age and whether or not they have comorbid diseases, such as heart disease and kidney disease. Very importantly, I also take into account the biology of the disease. For example, whether it’s a new presentation that we call de novo AML, whether the AML has occurred in the setting of a prior myelodysplastic syndrome, or whether the patients had prior chemotherapy for another cancer. Taking all these things into account, I determine what the best initial therapy is, and I’m also considering what the best subsequent therapy might be for a patient who achieves remission with whatever I give him or her initially.

For adults who are considered fit enough, number 1, and, number 2, likely to benefit from standard induction therapy, the standard induction therapy for good or ill hasn’t changed for the past 30 years. It’s commonly known as 3+7, or some people like to say 7+3 chemotherapy, which is 3 days of anthracycline, usually either daunorubicin or idarubicin, plus 7 days of a continuous infusional cytarabine. If 3 and 7 are given, a bone marrow should be done approximately 14 days after it starts to determine if another cycle of induction—which could consistently repeat 3 and 7, or 2 and 5, which is 2 days of anthracycline and 5 days of cytarabine—is to be given. About 30% of patients require a second induction course to achieve remission.

I would say the clinical utility of minimal residual disease monitoring in non-APL (acute promyelocytic leukemia) AML is highly controversial at the moment. How best to use it is dependent upon the geographic place that the doctor resides and the techniques used to measure MRD, or minimal residual disease, in AML. It certainly makes a lot of sense to get away from the only historic measurement of response we had, looking under the light microscopic and counting the blasts, which these more sensitive techniques, such as flow cytometry and gene sequencing, allow us to do. The problem is, we haven’t really nailed down how to use this. Just yesterday, I heard Dr. Goldstone from the UK make a very profound and clear-cut assessment of MRD, if it’s used to determine how well a patient’s responded after initial therapy. If a patient has MRD detectability, we know that their outcome after a stem cell transplant is inferior. So, should we do it? If they don’t have MRD detectability with a sensitive assay, maybe they don’t need a transplant. It becomes very confusing as to how to use this when making posttreatment decisions in AML.

Hervé Dombret, MD: In Europe, the standard induction therapy is still the so-called 7+3, so it’s not so different as compared to the conventional induction treatment in the United States. Maybe there are some differences in the dosage of anthracycline or cytarabine, but not that much. Maybe the most important difference is the use of idarubicin rather than daunorubicin as an anthracycline because idarubicin is very frequently used in Europe. Otherwise, the standard treatment is quite similar.

In AML, when you are giving induction treatment to a patient, your primary goal is to get complete remission. To get a complete remission is defined by the disappearance of the leukemic cells in the bone marrow, in the blood, and in other tissues when there is extramedullary disease, and is associated with the recovery of platelet counts and neutrophil counts in the blood. So, this is a definition of complete remission. It is very important to get complete remission as a first step to cure the patients. Recently, the problem of minimal residual disease emerged in other diseases, for instance, acute lymphoblastic leukemia. There is currently a lot of effort to try to measure the level of minimal residual disease in a patient with complete remission. There are several techniques to do that, and it could be very, very important in the next development to standardize these techniques in order to have a new definition of what is really a remission. Is it only a morphologic remission on microscope examination or do we need more? Do we need to have a molecular remission without any minimal residual disease, or flow remission when you are measuring minimal residual disease on the basis of flow cytometry?

Transcript Edited for Clarity