Clinical Response to Upfront Targeted Tyrosine Kinase Inhibitors among Patients with Myeloid/Lymphoid Neoplasms with Eosinophilia and Tyrosine Kinase Gene Fusion

Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase (TK) gene fusion (MLN-TK) comprise a group of rare disorders. The outcome of TK inhibitors (TKIs) in blast-phase disease and disease driven by TK fusion other than PDGFRA is not well described. We performed retrospective multicenter analysis of 42 patients. Upfront TKI resulted in excellent long-term outcomes in both chronic-and blast-phase disease.Introduction: Myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusion (MLN-TK) is an entity encompassed of a heterogeneous group of rare hematopoietic neoplasms that are driven by gene fusion involving PDGDRA/B, FGFR1,JAK2, FLT3 or ETV6::ABL1. Though patients presenting with chronic phase MLN-TK with PDGFRA fusion display a favorable outcome in response to upfront TK inhibitor (TKI) therapy, the outcomes of MLNs driven by other TK fusions are not well described. In this study, we aimed to critically analyze the treatment outcomes of patients with MLN-TK, focusing on the role of upfront TKIs in both chronic-and blast-phase diseases. Methods: The retrospective study included patients with confirmed MLN-TK from 3 centers and assessed demographic and clinical variables, treatment, and outcomes. Results: For ty-t wo patients with confirmed MLN-TK [ PDGFRA (n = 22), PDGFRB (n = 4), FGFR1(n = 10), JAK2 (n = 2); and FLT3 (n = 3)] were included. Fifteen of 25 (60%) chronic-phased patients received upfront TKI therapy had a long-term remission. Nine of 16 (60%) blast-phase patients with upfront TKIs also achieved complete remission and remained alive at a median follow-up of 20 months. All 3 patients with blast phase disease who received upfront chemotherapy without positive response did not respond to subsequent TKI therapy, emphasizing the importance of initiating TKI therapy early. Upfront TKI therapy was associated with longer overall survival in univariate analyses (HR, 0.054 [95% CI, 0.007-0.42]) and multivariate analyses (HR, 0.03 [95% CI, 0.002-0.47]). Conclusion: The outcomes of upfront TKI therapy are excellent for MLN-TK in both chronic and blast phases, regardless of gene abnormalities.