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ASCO 2021: Exploring the Molecular Architecture of Extramedullary AML

By: Vanessa A. Carter, BS
Posted: Friday, July 2, 2021

Somedeb Ball, MD, of the H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, and colleagues explored the mutational landscape of extramedullary acute myeloid leukemia (AML) to identify targetable mutations for potential personalized therapies. Presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, these investigators concluded that next-generation sequencing is crucial for these patients, as 52% had likely targetable mutations (Abstract 7024).

This retrospective study focused on the clinical and genomic data of 58 patients with extramedullary AML from the University of Miami, Memorial Healthcare System, and Moffitt Cancer Center. Data from next-generation sequencing were obtained from panels that examined 24 to 406 genes; TP53, IDH1, IDH2, KRAS, NPM1, NRAS, and KIT were among the 15 genes covered by every panel.

The median patient age at diagnosis was 62, and 55% of participants were male; 19 patients had leukemia cutis, and 34 had myeloid sarcoma. During relapse, extramedullary AML was identified in 60% of patients, and 31% had isolated extramedullary disease. A significantly worse median overall survival was observed in individuals with leukemia cutis (5.7 months) compared with myeloid sarcoma (21.9 months, P = .008).

Next-generation sequencing results were available for 48 patients, of whom 19 had data from an extramedullary site. Whether patients had leukemia cutis or myeloid sarcoma remained an independent prognostic factor for overall survival (P = .04) and European LeukemiaNet risk category. A targetable genomic mutation was identified in 52% of participants, the most common being mutations in IDH (37%) and NPM1 (21%), followed by MLL partial tandem duplications (11%) and FLT3 mutations (5%). Significant discordance in targetable mutations between extramedullary and nonextramedullary sequencing was observed in five patients, and three of four individuals who received an IDH1/2 inhibitor based on sequencing achieved a complete response.

Disclosure: For full disclosures of the study authors, visit coi.asco.org.


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