Abstract
ObjectiveTo explore the role of chidamide, decitabine plus priming regimen in the salvage treatment of relapsed/refractory acute myeloid leukemia.MethodsA clinical trial was conducted in relapsed/refractory acute myeloid leukemia patients using chidamide, decitabine, cytarabine, idarubicin, and granulocyte-colony stimulating factor, termed CDIAG, a double epigenetic priming regimen.ResultsThirty-five patients were recruited. Three patients received 2 treatment cycles. In 32 evaluable patients and 35 treatment courses, the completed remission rate (CRR) was 42.9%. The median OS time was 11.7 months. The median OS times of responders were 18.4 months, while those of nonresponders were 7.4 months (P = 0.015). The presence of RUNX1 mutations was associated with a high CRR but a short 2-year OS (P = 0.023) and PFS (P = 0.018) due to relapse after treatment. The presence of IDH mutations had no effect on the remission rate (80.0% vs. 73.3%), but showed a better OS (2-year OS rate: 100.0% vs. 28.9%). Grade 3/4 nonhematological adverse events included pneumonia, hematosepsis, febrile neutropenia, skin and soft tissue infection and others.ConclusionThe double epigenetic priming regimen (CDIAG regimen) showed considerably good antileukemia activity in these patients. Adverse events were acceptable according to previous experience. The study was registered as a clinical trial.Clinical Trial Registrationhttps://clinicaltrials.gov/, identifier:NCT03985007
Highlights
Treatment of Acute myeloid leukemia (AML) is rapidly progressing, approximately 10% to 40% of newly diagnosed AML patients cannot achieve complete remission (CR) through induction chemotherapy, and more than 50% of AML patients will relapse [1]
The presence of RUNX1 mutations was associated with a high completed remission rate (CRR) but a short 2-year overall survival (OS) (P = 0.023) and progression-free survival (PFS) (P = 0.018) due to relapse after treatment
The presence of IDH mutations had no effect on the remission rate (80.0% vs. 73.3%), but showed a better OS (2-year OS rate: 100.0% vs. 28.9%)
Summary
Treatment of Acute myeloid leukemia (AML) is rapidly progressing, approximately 10% to 40% of newly diagnosed AML patients cannot achieve complete remission (CR) through induction chemotherapy, and more than 50% of AML patients will relapse [1]. For patients with relapsed/ refractory (R/R) AML, the goal of chemotherapy varies from achieving long-term remission to providing a “bridge” to stem cell transplantation (SCT). Several new small-molecule inhibitors have been developed (e.g., ABT-199, midostaurin, and IDH1/2 inhibitor) and have shown promising results in R/R AML treatment, they are not currently commercially available in mainland China. Chidamide is the first subtype-selective oral histone deacetylation inhibitor (HDACi) commercially available in mainland China and has been certified internationally by the FDA because it is effective in treating R/R peripheral T-cell lymphoma (PTCL) [6]. Selective targeting of individual HDACs causes differentiation, apoptosis, cell cycle inhibition, migration inhibition, susceptibility to chemotherapy and anti-angiogenesis [7, 8]
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