A phase II study of venetoclax (VEN) in combination with 10-day decitabine (DEC) in older/unfit pts with newly diagnosed (ND) or pts with relapsed/refractory (R/R) acute myeloid leukemia (AML), or high-risk myelodysplastic syndrome (HR-MDS).

6549 Background: We report long-term results of phase 2 study of 10-day DEC and VEN (DEC10-VEN) in AML/HR-MDS. Methods: This single-institution study (NCT03404193) included intensive chemotherapy-ineligible pts >60y with ND de novo AML or secondary AML (sAML), or R/R AML, or HR-MDS. Induction therapy: DAC 20 mg/m 2 IV x 10d + VEN days 1-28. VEN was stopped on day 21 if bone marrow blasts ≤5%. Consolidation included DEC IV x 5 days + VEN days 1-21, every 4-8 weeks as previously described (DiNardo et al. Lancet Haem. 2020). Primary endpoint was ORR. Secondary endpoints are duration of response, OS, RFS, and safety. Here, we report an update with 232 pts and results of HR-MDS/CMML cohort. Results: 232 pts were enrolled thus far (ND AML-86; sAML-49; R/R AML-76; HR-MDS/CMML-21). Median follow up is 39 mo (36-46 mo). Median age was 73y in ND AML and 64y in R/R AML (Table). Three-fourths of pts inAML cohort were adverse risk by ELN 2022 risk. CR/CRi rates in ND AML, sAML, and R/R AML were 92%, 53%, and 40% and ORR was 88%, 69%, 58%, respectively. Median OS was 12.3 mo in frontline (FL, ND (16.7 mo) and sAML (10.4 mo)) and 7.6 mo in R/R. Similarly, median RFS was 9.1 (ND-10 mo and sAML-6.4 mo) and 7.5 mo, respectively. Median time to ANC ≥500 x 10 9 /L in cycle 1 was 41 days and Plt ≥50 x 10 9 /L was 31 days in FL pts. 30-day mortality was 2% in FL and 5% in R/R cohort. 18% in FL and 22% in R/R cohort proceeded to SCT. In HR-MDS cohort, the median age was 71y; 18/21 pts had prior treatment. ASXL1 was the most frequent mutation. ORR was 52% (CR+CRi-33%). Median OS-12.1, RFS-7.3 mo. Median time to ANC ≥500 x 10 9 /L was 55 and plt ≥50 x 10 9 /L was 51 days. Most common grade 3/4 AEs were infection with neutropenia (38%), febrile neutropenia (32%), thrombocytopenia (17%), and neutropenia (15%), consistent with HMA + VEN experience. Conclusions: DEC10-VEN demonstrated expected safety and efficacy in a particularly high-risk cohort of ND and R/R pts, with no evidence that 10-days of DEC provides improved responses over standard 5-days DEC. Clinical trial information: NCT03404193 . Table: see text