Assessing the role of venetoclax in combination with hypomethylating agents in higher risk myelodysplastic syndrome

Abstract Hypomethylating agents (HMA) remain the backbone of therapy for treating higher risk myelodysplastic syndromes (HR-MDS), however less than 20% of these patients achieve a complete remission (CR). Preliminary data have reported promising higher response rate combining HMA with Venetoclax as first line therapy (1L) as well as activity in HMA failure MDS. We identified 1193 higher risk MDS patients who received HMA as 1L therapy for HR-MDS, 1158 patients received 1L HMA alone and 35 patients received 1L HMA/Venetoclax combination. The overall response rate was 77% for 1L HMA/Venetoclax compared to 40% for 1L HMA alone (p<0.005). Among patients with ASXL1 mutation, CR were 44% and 8% for combination and HMA alone, respectively (p <0.005). Among patients with TP53 mutation, the overall response rate (ORR) was 75% and 44% for 1L HMA/Venetoclax and HMA alone respectively (p=0.038). The OS was 21 months and 20 months for 1L HMA/Venetoclax and 1L HMA alone respectively (p=0.86). For 269 patients who proceeded to transplant, the 2-year survival rates were 91% and 51% for 1L HMA/Venetoclax and HMA alone, respectively. Overall HMA/Venetoclax results in higher responses in both frontline and HMA failure patients with favorable outcomes in HMA patients bridged to AHSCT.