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

ABSTRACT

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.

KEYWORDS:

• Acute myeloid leukemia
• aml
• AML with myelodysplasia-related changes
• aml-mrc
• induction chemotherapy
• novel therapies
• secondary aml
• treatment

List of abbreviations

Acute Leukemia French Association (ALFA)

Acute myeloid leukemia (AML)

Allogeneic stem cell transplantation (allo-SCT)

Antecedent hematologic disorders (AHD)

Antibody-drug conjugates (ADCs)

Bi-specific T-cell engagers (BiTEs)

Complete remission (CR)

Complete remission with incomplete hematologic recovery (CRi)

Confidence interval (CI)

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)

Disease-free survival (DFS)

Dual-affinity retargeting (DART)

Eastern Cooperative Oncology Group (ECOG)

European Leukemia Net (ELN)

Event-free survival (EFS)

Fluorescence in situ hybridization (FISH)

Food and Drug Administration (FDA)

Gemtuzumab ozogamicin (GO)

Hazard ratio (HR)

Hypomethylating agent (HMA)

Intensive chemotherapy (IC)

Low-dose cytarabine (LDAC)

Measurable residual disease (MRD)

Morphologic leukemia-free state (MLFS)

Myelodysplasia-related changes (MRC)

Myelodysplastic syndrome (MDS)

Odds ratio (OR)

Overall survival (OS)

Partial remission (PR)

Programmed cell death protein 1 (PD-1)

Regulatory T-cells (Tregs)

Secondary AML (s-AML)

Small molecule immunomodulatory drug (IMiD)

Therapy-related AML (t-AML)

World Health Organization (WHO)

Declaration of interest

DFP has no competing interests. JFZ has served as a consultant for AbbVie and Takeda; has received honoraria from Agios/Servier, Bristol Myers Squibb, Daiichi Sankyo, Genentech, Gilead, Shattuck Labs and Takeda; has received research funding from Arog, Astex, Gilead, Merck, Sumitomo Dainippon Pharma and Takeda.