Chidamide in Combination With DCAG With or Without Venetoclax for Relapsed/Refractory Acute Myeloid Leukemia

Abstract

ABSTRACT Introduction Currently, there are only a few avaailable treatment options for patients with relapsed and refractory acute myeloid leukemia (R/R AML). Methods We conducted a single‐center, phase 1 prospective study (ChiCTR2200065634) to evaluate the efficacy and safety of chidamide, demethylating drugs (azacitidine), cytarabine, aclacinomycin, and G‐CSF plus venetoclax (CDCAG‐VEN) in patients with R/R AML. The previous CDCAG regimen was used as a historical control to compare its efficacy and safety. Thirty and 22 patients received one course of CDCAG with or without a 14‐day course of venetoclax, respectively. Results The overall response rate (ORR) was significantly higher in the CDCAG‐VEN group than in the CDCAG‐treated group (78.6% vs. 45.5%; p = 0.015), and the CDCAG‐VEN group achieved a better trend of measurable residual disease‐negative response (61.1% vs. 22.2%, p = 0.134). Compared with the CDCAG group, the CDCAG‐VEN group exhibited significantly better 1‐year overall survival (63.3% vs. 35.1%, p = 0.005) and progression‐free survival (76.7% vs. 36.0%, p = 0.022). The duration of response was notably better in the CDCAG‐VEN group than in the CDCAG group (71.2% vs. 34.3%, p = 0.021) and had a lower cumulative incidence of relapse (22.2% vs. 48.9%, p = 0.095). The neutrophil and platelet recovery times were similar between the CDCAG‐VEN and CDCAG groups (neutrophil: 18 days vs. 19 days, p = 0.293; platelet: 18 days vs. 19 days, p = 0.311). The frequencies of adverse events were comparable between both groups, except for a lower incidence of thrombosis in the CDCAG‐VEN group (0% vs. 22.7%, p = 0.006). Discussion In conclusion, venetoclax in combination with CDCAG is an effective and safe treatment regimen for R/R AML, thereby rapidly identifying chemosensitive patients and inducing measurable residual disease‐negative remission in a high proportion of patients with R/R AML.

Keywords

• acute myeloid leukemia
• chemotherapy
• conventional
• induction therapy
• Venetoclax