Maintenance Therapy with Chidamide Decreases the Relapse in Fusion Gene-Positive AML Patients with MRD-Positive or ELN-High Risk

Purpose: Acute myeloid leukemia (AML) patients with fusion gene-positive including core binding factor (CBF), mixed-lineage leukemia (MLL) gene rearrangement have a high incidence of relapse if they are continious measurable residual disease (MRD)-positive or in ELN-high risk and could not be bridged to allogenetic heamatopoitic stem cell transplantation (allo-HSCT). As known histone deacetylase (HDAC) is abnormally recruited in these fusion gene-positive AML, also RUNX1 mutated AML, and could be a therapy target. Aim of this study is to assess the effect and safety of HDAC inhibitor chidamide as maintemance therapy in these AML patients.

Methods: A multi-center retrospective study was performed. Patients with MRD-positive CBF-AML, MLL rearrangement or RUNX1 mutation AML, without being bridged to allo-HSCT were included. Maintemance with chidamide was started one to three months after consolidation for at least six months, at a dose of 10mg/day or 30mg twice a week.

Results: Twelve patients were enrolled, included 8 with AML1-ETO-positive, 3 with RUNX1 mutation, 1 with MLL rearrangement. The median age was 33(16-62) years old. The ratio of male to female was 6 to 5. They previously experienced median 6(4-8) cycles of chemotherapy, included one with allo-HSCT, one with autologous-HSCT. They were all maintemanced with chidamide, except one with chidamide plus sorafenib. Eleven patients were available for outcome assessment. With a median follow-up of 14(2-67) months, among the 9 patients with MRD-positive, 6(66.7%) achieved MRD-negative, 1 stable disease, 2 relapsed and died. The median time to achieved MRD-negative was 2.5(1-12) months. The other 2 patients was contenious MRD-negative. The cumulative incidence of relapse was 2/11(18.2%). The rate of MRD-nagetive was 8/11(72.7%). The mortality rate was 2/11(18.2%). During the maintemance, 4 patients underwent bone marrow suppression, including 2 with grade 3, 2 with grade 1/2. One patients had an anorexia of grade 2.

Conclusion: Maintenance therapy with chidamide might decrease the relapse in fusion gene-positive AML patients with MRD-positive or ELN-high risk, who could not take allo-HSCT, and prolong their survival, with a well toleration.

Key words: chidamide, maintenance, fusion gene, acute myeloid leukemia