How would you approach treatment in an older (>65), but fit patient with intermediate-risk AML, but with MRD persistence after induction with 7+3?

The presence of measurable or minimal residual disease (MRD) after induction chemotherapy, before allogeneic transplant or after transplant is associated with risk of relapse. (Araki et al. J Clin Oncol. 34:329-36) The detection and measurement of MRD by flow cytometry requires specific expertise in technique and interpretation. For a fit older adult with intermediate risk AML we typically consider allogeneic transplantation in CR1 if the patient is MRD negative. If after induction the patient is in CR1 by morphology, but is MRD positive we would consider a course of consolidation chemotherapy in an attempt to render the patient MRD negative. This typically might include intermediate-dose cytarabine. If after 1 course of consolidation the patient remains MRD positive we might proceed with transplant recognizing that there is still potential for cure, but the likelihood of cure is considerably less than if the transplant was carried out when the patient was MRD negative. If an MRD positive patient could not receive intensive consolidation one might consider a hypomethylating agent HMA), but there are no data to definitively establish the benefit in this circumstance. If an MRD positive patient has a targetable mutation such as IDH2 it is tempting to consider the oral inhibitor Enasidenib; however, there are no data to demonstrate the effectiveness of such an approach and the drug is not approved in this setting. It will be interesting to see how the strategies above will change if the promise, particularly in rendering patients MRD negative, of the combination of HMAs plus the Bcl2 inhibitor, Venetoclax is realized. (DiNardo et al. Blood. 133: 7-17)