Venetoclax plus Decitabine versus Intensive Chemotherapy for Treating Relapsed/Refractory AML

For older/unfit patients with newly diagnosed acute myeloid leukemia (AML), venetoclax plus azacitidine is the standard of care; however, data comparing venetoclax-based lower-intensity regimens with intensive chemotherapy (IC) as salvage are needed. Thus, this prospective phase 2 trial was a designed study that compared outcomes for 10-day decitabine + venetoclax (DEC10-VEN) with IC in a historical cohort using a propensity score–matched analysis, among adult patients with relapsed/refractory (R/R) AML.

The DEC10-VEN regimen consisted of decitabine 20 mg/m² daily for 10 days and venetoclax daily for induction, and 5 days of decitabine with venetoclax for consolidation. Patients with prior venetoclax exposure were excluded. In the IC arm, patients were selected from 2 prior phase 1b/2 trials where they had received any of the following 3 regimens: intravenous (IV) clofarabine 15 mg/m² daily on days 1 to 5, IV idarubicin 10 mg/m² daily on days 1 to 3, and IV cytarabine 1 g/m² daily on days 1 to 5 (CIA); IV cladribine 5 mg/m² on days 1 to 5, IV cytarabine 1 to 2 g/m² on days 1 to 5, and IV idarubicin 10 mg/m² on days 1 to 30 (CLIA); or IV fludarabine 30 mg/m² on days 1 to 5, IV idarubicin 10 mg/m² daily on days 1 to 3, and IV cytarabine 1 g/m² daily on days 1 to 5 (FIA).

A total of 54 patients who were treated with DEC10-VEN between January 2018 and December 2019 were matched with 54 patients who were treated with IC between February 2011 and January 2018. Baseline characteristics between the 2 cohorts were well-balanced. In the DEC10-VEN arm, the median age of patients was 62 years and the median age of patients in the IC arm was 59 years. In both arms, the median lines of previous therapy were 2. In the IC arm, 26 patients had received CLIA, 20 received CIA, and 8 had received FIA. The median follow-up was 12.5 months in the DEC10-VEN arm and 22.5 months in the IC arm. Patients in the DEC10-VEN arm received a median of 2 cycles of therapy, while patients in the IC arm received a median of 1 cycle.

In the DEC10-VEN arm, 41% of patients achieved complete response (CR) or CR with incomplete hematologic recovery compared with 30% in the IC arm (odds ratio, 1.40; 95% confidence interval [CI], 0.62-3.15; P = .47). The rates of primary refractory disease were 28% in the DEC10-VEN arm and 54% in the IC arm. In both arms, best response was achieved with a median of 1 cycle. The 30-day mortality was 7% (n = 3) in the DEC10-VEN arm and 9% (n = 5) in the IC arm. In the DEC10-VEN arm, median overall survival (OS) was 7.1 months compared with 5.5 months in the IC arm. A total of 10 patients in the DEC10-VEN arm and 8 patients in the IC arm moved on to allogeneic stem-cell transplantation (allo-SCT). Following allo-SCT, median OS was 19.3 months in the DEC10-VEN arm compared with 13.5 months in the IC arm (hazard ratio, 1.21; 95% CI, 0.35-4.22; P = .1).

In younger patients with R/R AML, the efficacy of DEC10-VEN as a salvage therapy is comparable to IC regimens that do not include venetoclax and is an appropriate bridge to allo-SCT. Further research is needed regarding the addition of novel therapies that may improve outcomes in R/R AML.

Reference

Abstract 637. ASH 2020. December 7, 2020. Ten-Day Decitabine with Venetoclax Versus Intensive Chemotherapy in Relapsed or Refractory Acute Myeloid Leukemia: A Propensity Score Matched Analysis.