Which are the most promising targets for minimal residual disease-directed therapy in acute myeloid leukemia prior to allogeneic stem cell transplant?

Abstract

Minimal residual disease has emerged as an important prognostic factor for relapse and survival in acute myeloid leukemia. Eradication of minimal residual disease may increase the number of patients with long-term survival; however, to date, strategies that specifically target minimal residual disease are limited. Consensus guidelines on minimal residual disease detection by immunophenotypic and molecular methods are an essential initial step for clinical trials evaluating minimal residual disease. Here, we review promising targets of minimal residual disease prior to allogeneic stem cell transplantation. Specifically, the focus of this review is on the rationale and clinical development of therapies targeting: oncogenic driver mutations, apoptosis, methylation, and leukemic immune targets. We review the progress made in the clinical development of therapies against each target and the challenges that lie ahead.

Figure 1.

Active clinical trials evaluating minimal residual disease-directed therapies arranged by trial design. Trials with induction and consolidation-based combinations are shown on the left, non-chemotherapy post-remission therapies are shown on the right. Studies evaluating post-allogeneic transplant minimal residual disease therapies are not included.