Emerging therapies for AML with myelodysplasia-related changes: slowly but surely moving the needle

Introduction: Patients with acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) have historically poor outcomes with conventional chemotherapy regimens. Current treatment strategies focus on intensive induction therapy followed by allogeneic stem cell transplant or a less intensive approach with hypomethylating agents with or without venetoclax. CPX-351 is a liposomal formulation of cytarabine and daunorubicin that has been shown to significantly improve response rates and survival compared with 7 + 3 (continuous infusion cytarabine plus anthracyclines). Despite the approval of CPX-351 for AML-MRC, overall prognosis remains poor with an unmet need to develop novel therapeutic strategies for this patient population. Areas covered: This article reviews the data for existing therapeutic options for patients with AML-MRC and the emerging therapies undergoing clinical trial development for this patient population. Expert opinion: The development of CPX-351 as a more effective induction therapeutic backbone for patients with AML-MRC presents an opportunity to investigate novel combination regimens in order to further improve outcomes. Promising emerging therapeutic modalities include immunotherapeutic strategies, small-molecule inhibitors and targeted agents. Unfortunately, there have been few clinical trials focusing on patients with AML-MRC with reliance instead on subgroup analyses. Clinical trials focused specifically on this patient population are urgently needed.

Automated summary

Patients with AML-MRC historically have poor outcomes with conventional chemotherapy regimens. Although CPX-351 has shown to significantly improve response rates and survival, there is still an unmet need for developing novel therapeutic strategies for this patient population. Emerging therapies such as immunotherapeutic strategies, small-molecule inhibitors, and targeted agents show promise in improving outcomes for AML-MRC patients, with a need for more clinical trials focused specifically on this population.