Venetoclax plus azacitidine is the standard of care for older/unfit patients with newly diagnosed acute myeloid leukemia (AML), but data are needed comparing venetoclax-based lower-intensity regimens with intensive chemotherapy (IC) as salvage in adult patients with AML. This study compared outcomes for adult patients with relapsed/refractory (R/R) AML treated with 10-day decitabine plus venetoclax (DEC10-VEN) in a prospective phase 2 trial versus IC in a historical cohort using a propensity score–matched analysis.
The DEC10-VEN regimen was comprised of decitabine 20 mg/m2 daily for 10 days, plus venetoclax daily for induction, followed by 5 days of decitabine with venetoclax for consolidation; patients with prior exposure to venetoclax were excluded. Patients in the IC cohort had received any of the following regimens in 2 previous phase 1b/2 trials: intravenous (IV) cladribine 5 mg/m2 on days 1 to 5, IV cytarabine 1 g/m2 to 2 g/m2 on days 1 to 5, and IV idarubicin 10 mg/m2 on days 1 to 30 (CLIA); 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); 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 54/55 patients treated with DEC10-VEN between January 2018 and December 2019 were determined to best match with 54/197 patients treated with IC between February 2011 and January 2018; baseline characteristics were well balanced between the 2 cohorts. The median age of patients in the DEC10-VEN cohort was 62 years versus 59 years for the IC cohort. Patients in both cohorts had received a median of 2 prior lines of therapy. CLIA, CIA, and FIA were received in 26, 20, and 8 patients in the IC group, respectively. The median follow-up was 12.5 months and 22.5 months for the DEC10-VEN and IC cohorts, respectively. Patients received a median of 2 and 1 cycles of therapy in the DEC10-VEN and IC cohorts, respectively.
A total of 41% and 30% of patients achieved complete response (CR) or CR with incomplete hematologic recovery with DEC10-VEN versus IC, respectively (odds ratio, 1.40; 95% confidence interval (CI), 0.62-3.15; P = .47). The rates of primary refractory disease were 28% and 54% with DEC10-VEN and IC, respectively. Best response was achieved with a median of 1 cycle in both cohorts. The 30-day mortality was 7% (n = 3) and 9% (n = 5) with DEC10-VEN versus IC, respectively. The median overall survival was 7.1 months versus 5.5 months with DEC10-VEN versus IC, respectively. Ten and 8 patients in the DEC10-VEN and IC cohorts, respectively, proceeded to allogeneic stem-cell transplantation (allo-SCT). The median overall survival after allo-SCT was 19.3 months and 13.5 months in the DEC10-VEN and IC cohorts, respectively (hazard ratio, 1.21; 95% CI, 0.35-4.22; P = .1).
The efficacy of DEC10-VEN is comparable to non-venetoclax–based IC regimens as a salvage therapy in younger patients with R/R AML and is an appropriate bridge to allo-SCT. Furthermore, the addition of novel therapies may improve efficacy and deserves further study in the R/R setting in this malignancy.
Reference
Maiti A, DiNardo C, Kadia TM, et al. Ten-Day Decitabine with Venetoclax versus Intensive Chemotherapy in Relapsed or Refractory Acute Myeloid Leukemia: A Propensity Score Matched Analysis. Presented at: 62nd American Society of Hematology Annual Meeting & Exposition, December 5-8, 2020. Abstract 637.