P080 | OBSERVATIONAL MONOCENTRIC STUDY ON VENETOCLAX-BASED THERAPY IN ACUTE MYELOID LEUKEMIA: ROLE OF CR/CRI ACHIEVEMENT AND DRUG INTERACTIONS ON SURVIVAL

Venetoclax (VEN) and hypomethylating agents (HMAs) showed efficacy both in patients with newly diagnosed acute myeloid leukemia (AML), and in patients refractory or relapsed after previous intensive chemotherapeutic lines, even after allogeneic hematopoietic stem cell transplantation (HSCT). Current research is evaluating VEN and HMAs as new backbones for combination regimens, and as a bridge to allogeneic hematopoietic stem cell transplantation (HSCT) in fit patients. Posaconazole antifungal prophylaxis (AFP) is reccomended during first cycles of VEN-HMAs, requiring VEN dose reductions, that are variably applied in clinical practice in a range from 50 mg to 100 mg, based on pharmacokinetic studies. We report here the efficacy and safety of VEN-HMAs combination therapy in 38 first-line (FL) and 51 relapsed-refractory (R/R) AML patients. In FL pts, 14/38 (37%) and 12/38 (31%) achieved CR and CRi, respectively. In R/R pts, 17/51 (33%) and 8/51 (16%) achieved CR and CRi, respectively. Although composite complete remission (cCR) rate was lower in R/R than in FL (49% vs 68%, respectively; p = 0.08), achievement of this status was associated with comparable overall survival (OS) in R/R and FL (13.7 vs 14.5 months, respectively). Eighteen (20%) patients underwent HSCT after obtaining cCR, with a 2-year OS probability of 63%. AFP was associated with a lower rate of grade 3-4 fungal infections (6% vs 24%, p = 0.024), but reduced VEN daily dose of 50 mg due to posaconazole was associated with significantly shorter PFS and OS in multivariate analysis. Previous exposure to HMAs was also associated with significantly shorter survival. Furthermore, pts achieving CR had significant better OS than CRi pts (p<0.0001)(Fig.1). In conclusion, AML patients treated with VEN-HMAs and achieving cCR, presented comparable OS both in R/R and FL and had a significant rate of alloHSCT bridging. AFP reduces the risk of fungal infections, but the observed shorter PFS and OS in pts treated with VEN reduced dose to 50 mg deserve further attention in future studies. Finally, pts obtaining CR had significantly better OS compared to CRi patients.