Abstract
The management of patients with relapsed or refractory (R/R) acute myeloid leukaemia (AML) remains a challenge with few reliably effective treatments. Chidamide, a new selective HDAC inhibitor, has demonstrated some effectiveness in AML patients. Herein, we reported three patients with R/R AML who were unresponsive to venetoclax plus azacitidine (VA) but were successfully treated with VA when chidamide was added to the regimen. MCL1 is one of the anti-apoptotic proteins. Chidamide targets the MCL1 protein, which may permit venetoclax resistance when upregulated. We determined MCL1 protein expression in different AML cell lines, and chidamide could downregulate MCL1 expression in venetoclax resistance AML cells. In general, our experience showed that the chidamide/VA combination could improve the condition of R/R AML patients who are resistant to VA. Formally evaluating this regimen in R/R AML patients may be meaningful.
Highlights
acute myeloid leukaemia (AML) is a disease caused by the blocked differentiation of myeloid haematopoietic stem cells and the clonal proliferation of primitive or immature myeloid cells in the bone marrow (BM)
To further determine that chidamide could downregulate myeloid cell leukaemia 1 (MCL1) and overcome venetoclax resistance, we evaluated antiapoptotic protein expression in different tested AML cell lines which were purchased from ATCC (Manassas, US)
These findings suggest that chidamide may induce venetoclax-resistant leukaemia suppression by downregulating MCL1, which could be further exploited in future clinical trials
Summary
AML is a disease caused by the blocked differentiation of myeloid haematopoietic stem cells and the clonal proliferation of primitive or immature myeloid cells in the bone marrow (BM). Venetoclax combined with azacitidine [VA, venetoclax once daily (100 mg day 200 mg day 400 mg day3-28) and azacitidine 75 mg/m2 day1-7.] was administered as a salvage therapy, an effective regimen recommended for the treatment of R/R AML patients who are ineligible for intensive salvage chemotherapy, but progressive disease was observed. The patient achieved CR after 1 cycle of the IA regimen [idarubicin 12 mg/m2 day, cytarabine 100 mg/m2 continuous infusion day1-7.] and received 6 courses of the HiDAC regimen [cytarabine 2 g/m2 over 3 h every 12 h on day1–3.] as consolidation therapies while not adopting allogeneic haematopoietic stem cell transplantation The patient experienced his first relapse 2 years after first remission with a 9% immature cell level in the BM and was treated with the CAG [cytarabine 10 mg/m2 every 12 h, day; aclarubicin 5-7 mg/ m2, daily on day; and concurrent use of G-CSF 200 μg/m2/ day.] regimen for 3 cycles, resulting in a second CR in March 2019. After 1 month of follow-up, the patient remains in CR at the time of writing
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