PB2183: RELAPSE PREDICTS POOR OUTCOMES IN FLT3-MUTATED ACUTE MYELOID LEUKEMIA POST ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION

Abstract

Background: Allogeneic hematopoietic cell transplantation (alloHCT) is the only curative option for patients with FLT3-ITD (FMS-like tyrosine kinase 3 internal tandem duplication) acute myeloid leukemia (AML). Although sorafenib has been recommended as maintenance treatment, data on risk factors and outcomes in these patients are limited. Aims: We investigated the risk factors and outcomes in patients with FLT3-mutated AML that underwent alloHCT. Methods: We enrolled consecutive adult patients with FLT3-mutated AML that underwent alloHCT at our JACIE-accredited center over the last two decades based on EBMT standards. The following factors were recorded and analyzed: age, disease, phase at transplant, type of donor and transplant, grade II-IV acute and moderate/severe chronic graft-versus-host disease (GVHD), relapse, treatment-related mortality (TRM), disease-free (DFS) and overall survival (OS). Results: We studied 43 patients with FLT3-mutated AML who received alloHCT at a median age of 45 (18-62) years from sibling (21), matched (16) or mis-matched (3) unrelated, and haploidentical donors (3). Phase at transplant was first complete remission/CR1 (31 patients), CR2 (9) or relapsed/refractory disease (3). With a median follow-up of 26.5 (1.2-239) months, relapse was observed in 16 patients, 4 of whom presented only with isolated extramedullary disease. Five-year cumulative incidence (CI) of relapse was 41.7% and was independently associated with previous lines of treatment (p=0.015), disease phase at transplant (25.7% for CR1, 50% for CR2, and 100% for relapsed/refractory disease, p=0.007), and chronic GVHD (p=0.004). Relapse was treated with chemotherapy (15 patients), donor lymphocyte infusions (7), azacytidine (6), or gilteritinib (3). No patient received sorafenib either as maintenance or treatment. Only one relapsed patient survived after treatment of isolated extramedullary disease. Five-year CI of TRM was 17.4% and was associated only with disease phase at transplant (p<0.001). Five-year DFS and OS were 46.5% and 52.5%, respectively. The only significant predictor of OS was relapse (beta=0.303, p<0.001). Summary/Conclusion: r study confirms that relapse post alloHCT is an imminent feature of FLT3-mutated AML, associated with poor outcomes. Disease phase at transplant is an important risk factor for alloHCT outcomes. Nevertheless, relapse incidence remains high, even in patients transplanted in CR1, highlighting the necessity of maintenance therapy with FLT3 inhibitors.