Outcomes of 10-day decitabine with venetoclax for AML.

Abstract

7022 Background: Venetoclax (VEN) + a hypomethylating agent (HMA) has improved outcomes for patients with acute myeloid leukemia (AML). VIALE-A showed improved overall response rate (ORR) and overall survival (OS) with VEN + HMA in newly diagnosed AML (ND AML); the complete remission (CR) rate was 36.7% and the median OS was 14.7 months. Later, DiNardo et al. reported a trial of 10-day decitabine (DEC10) + VEN with a CR rate of 65.7% and a median OS of 18 months in a ND AML cohort. We report real world outcomes of VEN + DEC10 for AML induction. Methods: We reviewed 82 adult patients treated with VEN + DEC10 at our institution. Patients received 1 or 2 cycles of VEN + DEC10 followed by additional cycles of VEN + 5-day decitabine (DEC5) per physician discretion. Results: Twenty-four patients had ND AML, 28 had secondary AML (sAML) and 30 had relapsed/refractory (R/R AML) with a median age (years) of 72, 70, and 59 in each group, respectively. Cytogenetics were poor-risk in 13 ND patients (54.2%), 14 sAML patients (50%), and 17 R/R patients (56.7%). Twenty-two patients (26.8%) had TP53 mutations. Six patients (7.3%) received rasburicase. Neutropenic fever was seen in 46 patients (56.1%), and 34 (41.5%) had documented infections. Thirty-eight patients (46.3%) were re-hospitalized during cycle 1 (C1), at a median of 22 days after starting. The median time from the start of C1 to C2 was 41 days. Thirty-day mortality was 7.3%. In ND AML, ORR was 91.7% and composite CR rate (CRc; CR + CR with incomplete hematologic recovery[CRi]) was 75%. Nine of 15 patients (60%) in CR were negative for measurable residual disease (MRD-). In sAML, ORR was 53.6% and CRc rate was 50% (35.7% MRD- CR). CRc was achieved by eight of 16 (50%) untreated sAML patients vs six of 12 (50%) who were previously treated. In R/R AML, ORR was 56.7% and CRc rate was 43.3% (53.8% MRD- CR). TP53-mutated AML had an ORR of 59% and a CRc of 50%. Median OS was 5.5 months in TP53-mutant AML, 7.4 months in R/R AML, and was not reached in ND AML or sAML. Fifteen patients (18.3%) received an allogeneic transplant (3 ND, 3 sAML and 9 R/R) in MRD- CR (n = 11), MRD+ CR (n = 2) and CRi (n = 2). At a median of 263 days post-transplant, there were 3 relapses and the median OS was not reached. Conclusions: VEN + DEC10 compared favorably with published data, yielding high ORR, CR, and MRD- CR rates in ND AML. CR rate for R/R AML with VEN + DAC10 was similar to that for ND AML in the VIALE-A trial. These results warrant a prospective, randomized trial of VEN + DEC10 vs VEN + DEC5 in AML. [Table: see text]