Phase 2 study of azacitidine (AZA) and venetoclax (VEN) as maintenance therapy for acute myeloid leukemia (AML) patients in remission.

e19018 Background: Most patients (pts) with AML achieve remission with current therapies but rates of relapse are high. Maintenance with oral AZA (CC-486) has been shown to prolong overall survival (OS) and relapse-free survival (RFS) in SCT-ineligible patients with AML in remission. The addition of VEN to maintenance regimens should be explored. Methods: We designed a phase 2, single-center, single-arm study to evaluate the efficacy and tolerability of AZA + VEN maintenance in AML. Pts ≥ 18 years in first remission (CR1) after induction and 1+ consolidations not immediately eligible for SCT were treated with AZA 50 mg/m2 IV/SQ on D1-5 and VEN 400 mg on D1-14 (or D1-7 at physician discretion) every 28 days, up to 24 cycles. Pts in CR2 and beyond were eligible if positive for minimal residual disease (MRD). Both intensive (INT; int/high dose cytarabine-based) and low-intensity (LOW; HMA/LDAC-based) induction regimens were permitted, including prior VEN. The primary outcome was modified RFS (mRFS; enrollment to relapse or death). Key secondary objectives were OS (enrollment to death), safety, and MRD clearance. Results: As of Feb 10 2022, 33 pts have been enrolled (characteristics in Table). The median number of cycles given is 6 (range 1-23). 20 pts (61%) received 7 days and 13 (39%) received 14 days of VEN. To date, 8 relapses and 6 deaths (all after relapse or SCT) have occurred. 5 pts (15%) have gone off protocol for SCT (censored at time of SCT). Median mRFS is not reached (NR) in both the INT and LOW cohorts (1-yr mRFS 73.9% and 58.3%, respectively). When stratified by ELN 2017, mRFS was NR, NR, and 4 mo for favorable, intermediate, and adverse risk, respectively (6-mo mRFS 92.3%, 90%, and 44.4%). Median OS is NR in both the INT and LOW cohorts (1-yr OS 93.8% and 53.3%, respectively). mRFS was numerically higher in pts with VEN exposure as part of their induction regimen (1-yr mRFS 79.1% vs 55.6% in non-VEN-exposed pts, p=0.067). Of the 7 MRD(+) pts at enrollment, 2 (29%) cleared their MRD on AZA/VEN maintenance. MRD(+) pts had a median mRFS of only 4 mo compared to NR in the MRD(-) pts (p=0.001). The MRD(+) pts in our study were very high risk (5/7 ELN adverse, 3/7 complex karyotype). The most common grade 3/4 AEs were infections (18%), thrombocytopenia (15%), neutropenia (12%), and neutropenic fever (6%). 4/33 pts (12%) required C2 VEN dose reduction for cytopenias. Conclusions: AZA/VEN maintenance is effective and tolerable in AML pts not immediately eligible for SCT after intensive or low-intensity induction. The regimen yields encouraging mRFS and OS durations. Longer follow-up and comparative studies are needed to confirm these initial results. Clinical trial information: NCT04062266. [Table: see text]