The combination of hypomethylating agents (HMAs) with venetoclax (VEN) has been identified as a new treatment strategy for older patients with acute myeloid leukemia (AML). However, data are lacking on (1) how HMA + VEN compares with intensive chemotherapy (IC) in “fitter” patients and (2) objective outcomes with HMA + VEN for patients considered high risk for treatment-related mortality (TRM). The aims of the current study were to compare outcomes among older patients with AML receiving decitabine (DEC) + VEN for 10 days (DEC10 + VEN) versus IC, both overall and when stratified by IC “fitness” using a validated TRM risk model.
DEC10 + VEN therapy consisted of 10 days of DEC 20 mg/m2 plus daily VEN for induction, and 5 days of DEC + VEN as consolidation. Patients in the IC cohort were treated with regimens containing ≥1 g/m daily of cytarabine between 2000 and 2018 at a single institution. Exclusion criteria included European LeukemiaNet (ELN) favorable cytogenetics. Patients were classified as high risk for TRM with IC based on a validated TRM score (TRMS) incorporating 8 clinical variables with a cutoff value of >13.1. Propensity score matching (PSM) was used for 1:2 matching based on age, Eastern Cooperative Oncology Group (ECOG) performance status (PS), ELN risk group, and high (>13.1) versus low TRMS.
A total of 85 patients were enrolled in the DEC10-VEN group, with a median age of 72 years. Five percent of patients had ECOG PS ≥3, 65% had ELN adverse-risk disease, 28% had high TRMS, and 15% received allogeneic stem-cell transplantation (allo-SCT). A total of 170 patients were included the IC cohort, with a median age of 67 years. Seven percent of patients had ECOG PS ≥3, 58% had ELN adverse-risk disease, 28% had high TRMS, 18% received allo-SCT, and 62% had been treated on a clinical trial. The median follow-up was 16 months in the DEC10-VEN group and 55 months in the IC cohort.
Overall, DEC10-VEN led to superior rates of complete response (CR; including CR with incomplete hematologic recovery [CRi]), lower TRM, and longer overall survival (OS) versus IC. Indeed, CR/CRi rates were 82% and 59% with DEC10-VEN versus IC, respectively (odds ratio [OR], 3.19; 95% confidence interval [CI], 1.65-6.16; stratified P = .001). The 30-day mortality was 1.2% and 15% with DEC10-VEN versus IC, respectively (OR, 0.07; 95% CI, 0.01-0.49; stratified P = .008). The median OS was 15.1 months and 9.1 months with DEC10-VEN in the low and high TRMS groups, respectively. When stratified by TRM risk, patients at high risk for TRM experienced superior outcomes with DEC10-VEN versus IC, but outcomes for patients at low risk for TRM were similar with DEC10-VEN versus IC.
Superior outcomes were observed for older patients with AML receiving DEC10-VEN versus IC in a PSM analysis, particularly for those at high risk for TRM.
Maiti A, DiNardo C, Kadia T, et al. Abstract S141. EHA 2020. June 12, 2020. 10-Day Decitabine and Venetoclax (DEC10-VEN) vs. Intensive Chemotherapy (IC) in Acute Myeloid Leukemia (AML): A Propensity Score Matched Analysis Stratified by Risk of Treatment-Related Mortality. Presented at: 25th European Hematology Association Congress Virtual; June 11-21, 2020. Abstract S141.