Azacitidine and Venetoclax for High-risk MDS Patients | Jacqueline S. Garcia, MD | ASH 2023

Hi, I'm Jacqueline Garcia. I'm a medical oncologist at Dana-Farber Cancer Institute in Boston, Massachusetts. I treat myelodysplastic syndrome along with acute leukemias. At this year's American Society of Hematology meeting in 2023 in San Diego, I had the opportunity to present and share with my colleagues data from an ongoing phase 1b clinical trial that includes azacytidine plus venetoclax, the oral BCL2 inhibitor, for frontline therapy in high-risk MDS patients. In this presentation, we gave the update on responses and survival in patients that received the combination therapy at the recommended phase 2 dose. Separately, there is an ongoing study that is phase 3 randomized double-blinded using this very regimen versus azacytidine placebo. So this is the phase 1b single-arm data just to give a prelim information on what's going on and how patients are looking. So I presented on 107 patients with high-risk MDS. Eighty-five percent had IPSSSR, high or very high risk, so it was a high-risk cohort. We had patients with mutations in ASXL1, RUN-X1, and P53. SRSF2 is being the most frequent, so traditional MDS mutations. And the majority of patients had well over 5% or 10% bone marrow blasts on study entry. So this is a traditional high-risk MDS patient cohort. In this clinical trial, patients received azacytidine, 75 milligrams per meter squared for seven days each 28-day cycle, plus venetoclax, 400 milligrams days 1 through 14 with a two-week break. So what we were able to present is that safety looks great. There were expected lower blood counts that is expected with this regimen. There was a 42% febrile neutropenia event rate. There were infections that were observed. So what we did in this protocol to prevent these expected fevers and potential infection risk from becoming serious is we mandated antibacterial prophylaxis for patients with grade 3 or higher neutrophil count decreases. And that really helped to reduce severity of infections, making this regimen tolerable with the antibiotic prophylaxis plus interruptions to the venetoclax dosing as necessary. How did the outcomes look? Well, the complete remission rate by IWG 2006 criteria was 30%, which is fantastic. We did see additional responses, including marrow complete remission with hematologic improvement in 37%. We also observed transfusion independence conversion in well over 40% of patients. Importantly, when we took a look at the 107 patients and their median overall survival, it was at 26 months, which is fantastic. For patients in complete remission, the survival has not been reached, which is phenomenal. The median duration of complete remission is about 16 and a half months. So we were pleased to present the safety data. No new or unexpected issues were observed, and we were able to present the outcome data from the Phase 1B trial. We look forward to seeing what happens in the ongoing Phase 3 study, but we have some promising data already in the Phase 1 setting. Thank you.