Molecular annotation of extramedullary acute myeloid leukemia identifies high prevalence of targetable mutations

Background Genomic landscape of extramedullary acute myeloid leukemia (EM‐AML), including myeloid sarcoma (MS) and leukemia cutis (LC), is not well characterized. The potential utility of next‐generation sequencing (NGS) using EM tissue is not established. Methods In this multicenter retrospective study, clinical and NGS data were collected on patients with EM‐AML. All statistical analyses were performed in SPSS Statistics (v 26). Results Our study included 58 patients with EM‐AML. The median age at diagnosis was 62 years; 59% of patients had MS and 33% had LC. EM‐AML was isolated (i.e., without blood or marrow involvement) in 31% and was first noted at relapse in 60% of patients. Median overall survival in our cohort was 18.2 months overall, with 19.1 months and 11.6 months in the newly diagnosed and the relapsed/refractory patients, respectively. At least one targetable or potentially targetable alteration was present in 52% of patients with EM‐site NGS, with 26% IDH1, 21% NPM1, 11% IDH2, 6% FLT3, and 13% KMT2A‐PTD. Mutations in IDH1 were significantly more prevalent on NGS from EM tissue than non‐EM (blood or marrow) samples (26% vs. 3%; p = .030). Three of four patients treated with IDH inhibitors based on EM‐site NGS experienced a complete response. Conclusions Targetable mutations are frequent in EM‐AML and EM‐site NGS is warranted for selecting potential targeted therapies for patients with EM‐AML. Next‐generation sequencing (NGS) on extramedullary (EM) tissue revealed at least one potentially targetable alteration in 52% of patients with EM acute myeloid leukemia treatment with IDH inhibitors led to complete response in three of four patients with IDH1 or IDH2 mutations identified on EM‐site NGS.