7024 Background: Extramedullary (EM) involvement, including myeloid sarcoma (MS) and leukemia cutis (LC), is uncommon in patients with acute myeloid leukemia (AML). Mutational landscape of EM-AML is not well characterized, including concordance of sequencing data from EM vs. non-EM site (blood or bone marrow) and the potential for personalized targeted therapy in this patient cohort. Methods: In a multicenter retrospective study, clinical and genomic data were collected on EM-AML patients treated at Moffitt Cancer Center, Memorial Healthcare System, and University of Miami, as well as sequenced cases at a central laboratory. Next generation sequencing (NGS) data come from panels that interrogated 24- 406 genes, with 15 genes covered by all panels, including notably, IDH1, IDH2, KIT, KRAS, NPM1, NRAS, and TP53. Survival estimates using Kaplan-Meier statistics and multivariate analysis with Cox-regression were performed in SPSS (v.26). Results: Our study included 58 patients with EM-AML. Median age at diagnosis was 62 years; 55% of patients were males. In our cohort, 34 (59%) patients had MS, and 19 (33%) had LC. EM-AML was noted during relapse in 60% of evaluable patients (n=45), and 31% had isolated EM disease. Patients with LC had a significantly worse median overall survival (OS) than those with MS (5.7 months vs. 21.9 months, p= 0.008); Pattern of EM involvement (MS vs. LC) remained an independent prognostic factor for OS (p= 0.04) in a multivariate analysis including disease setting (new diagnosis vs. relapse) and ELN risk category. Results of NGS performed during EM presentation were available in 48 patients, 19 of which had NGS data from EM site. Most commonly mutated genes were NRAS on EM site NGS (37%) and NPM1 on non-EM site NGS (28%). Based on EM NGS, 52% patients had a targetable genomic alteration, with 37% mutations in IDH, 21% NPM1, 5% FLT3, and 11% MLL-PTD. Five (two with concurrent M+EM disease) out of nine evaluable patients had significant discordance in targetable mutations between EM and non-EM NGS at EM-AML. Three of four patients who received treatment with IDH1/2 inhibitors based on EM NGS achieved complete response. Conclusions: EM-AML has a distinct molecular architecture with an inferior OS in LC vs. MS patients. We conclude that EM site NGS is critical in patients with EM-AML, as 52% have potentially targetable mutations and could benefit from specific targeted therapies.[Table: see text]
Multiplex approach in classification, diagnosis, and prognostication in acute myeloid leukemia: An experience from tertiary cancer center in South India
