Personalized Molecular Phenotyping May Help Secondary AML

Personalized molecular phenotyping in the coming months and years should lead to a better understanding of risk mitigation strategies to help improve outcomes in patients with secondary acute myeloid leukemia (AML), according to Jeffrey E. Lancet, MD, of the Moffitt Cancer Center & Research Institute in Tampa, Florida. At the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 1–5 in Chicago, an educational session was held that reviewed core binding factor (CBF)-AML (the good), secondary AML (the bad), and TP53-mutated AML (the ugly). The section entitled, “The Bad: Secondary Leukemias-How Bad Are They?”, was presented by Dr. Lancet. He noted that new emerging tailored therapies are on the horizon.

Secondary AML is a subgroup of AML that is marked by treatment resistance and poor outcomes. Secondary AML is a composite designation and often includes AML that has developed in the context of a prior myeloid malignancy. Various biologic features contribute to this phenotype. However, Lancet said a much better understanding of this entity is now leading to the development of new molecular agents that could improve outcomes.

Lancet said the US Food and Drug Administration (FDA) approval of CPX-351 for the treatment of newly diagnosed therapy-related AML (t-AML) and AML with myelodysplastic syndrome (MDS)-related changes marks an important step forward. CPX-351 is a liposomal encapsulation of cytarabine and daunorubicin. Lancet said this unique system allows for improved drug delivery and prolonged exposure. A phase III trial showed that CPX-351 treatment resulted in significantly improved overall survival (9.56 vs 5.95 months), event-free survival (P = .021), and complete remission, plus complete remission with incomplete marrow recovery (47.7% vs 33.3%).

David Sallman, MD, of the malignant hematology department at Moffitt, said an improved classification system and better stratification of AML patients may help lead to improvements in outcomes. The 1997 World Health Organization classification of hematopoietic and lymphoid neoplasms created new categories. It separated secondary AML from de novo AML. The current classification of AML includes AML with recurrent genetic abnormalities, AML with multilineage dysplasia, t-AML and MDS, and AML not otherwise categorized.

“We have a relatively comprehensive understanding of the molecular architecture of secondary AML,” Sallman said. “We now need to try to develop more personalized therapies for these patients. There have been some major strides, but we still have a long way to go.”