MPN-521 Somatic Mutational Landscape and Clinical Response to Upfront Targeted Tyrosine Kinase Inhibitors Among Patients With Myeloid and Lymphoid Neoplasms With Eosinophilia and Rearrangements of PDGFRA, PDGFRB, FGFR1, JAK2, or FLT3.

CONTEXT: In 2016, WHO put together a category of myeloid and lymphoid neoplasms with eosinophilia (MLN-Eo) with rearrangement of PDGFRA, PDGFRB, FGFR1, or PCM1-JAK2. Gene fusions involving FLT3 and JAK2 are considered potential provisional entities. Here, we describe the mutational landscape of MLN-Eo and clinical outcomes of upfront targeted TK inhibitor (TKI) therapy.

DESIGN: We retrospectively reviewed clinical and molecular data on patients with MLN-Eos. Next-generation sequencing was performed using a customized or commercially available panel.

RESULTS: Twenty-three patients had PDGFRA fusion or activating mutations; 4 PDGFRB fusion; 8 FGFR1 fusion; 2 JAK2 fusion; and 4 FLT3 fusion. Twelve (92%) had at least one other coexisting mutation. At least 2 patients harbored TET2, RUNX1, TP53, and PTPN11 mutations. Pathogenic PTPN11 mutation was present in all activating PDGFRA mutations but absent in other cases. Among 23 patients with the chronic-phase disease, 14 (61%) received upfront TKI. None transformed into blastic phase. Six patients with disease in the de novo blastic phase received upfront TKI and achieved complete remission. Upfront TKI use was associated with longer overall survival (OS) in univariate analysis (HR 0.065, 95% CI, 0.008-0.50. P =.008). The improved OS remained significant in a multivariate analysis (HR 0.043, 95% CI, 0.003-0.63, p = 0.021) when adjusted for sex, age, hypereosinophilia, PDGFRA/B fusion, complex cytogenetics, the blastic- phase, and transplant status.

CONCLUSIONS: Patients with MLN-Eo have high frequency of secondary somatic mutations like other myeloid malignancies. TKI therapies are associated with excellent outcomes and should be used in the upfront setting.