Venetoclax and Azacitidine for Newly Diagnosed Non-Elderly Adult Patients with Acute Myeloid Leukemia and Adverse Risk Features

Background: Venetoclax (ven)+azacitidine (aza) is the standard of care for untreated acute myeloid leukemia (AML) patients (pts) ≥75 years or unfit for intensive induction chemotherapy (IC) due to comorbidities. While the standard of care for younger newly diagnosed pts is IC, long term outcomes for all but favorable risk pts are suboptimal. Specifically, pts with adverse risk disease, per the European Leukemia Network (ELN), are more likely to be refractory to IC and have low rates of long term survival. Ven based regimens have a ~70% response rate in the upfront setting; in contrast to IC, those with adverse risk do not have lower response rates. This study explores the feasibility and outcomes of ven+aza for newly diagnosed younger AML pts who are not necessarily unfit for IC, but carry adverse risk features that make them less likely to respond to this therapy. Methods: This is an interim analysis of an ongoing phase 2 study (NCT03573024) of a planned 36 untreated adverse risk AML pts 18-59. Pts have adequate organ function and white blood cell counts Results: 8 have enrolled between November 2018 and July 2020; median age is 33 (22-52). All have adverse risk disease (Table 1). There were 179 adverse events (AEs); 35 related. The ≥grade 3 events were: fatigue (N=1), leukopenia (N=2), neutropenia (N=2), anemia (N=2), thrombocytopenia (N=1). There were no deaths in the first 60 days. In cycle 1 pts spent a median 10 days (4-19) inpatient and required a median of 2 (0-10) red blood cell transfusions and 3 (0-15) platelet transfusions. Six of 8 (75%) pts responded; all 6 were CRs. 4/6 responses were cytogenetic remissions, 5/6 were MRD negative by MFC and 1/6 was MRD negative by ddPCR. Two pts relapsed, 35 and 84 days after remission; one was successfully salvaged with IC and proceeded to transplant while the other was refractory to IC and died from AML. Two pts were refractory to ven+aza; both were successfully salvaged with IC and have proceeded to transplant. 7/8 proceeded to transplant; 4 required only ven+aza for this outcome and proceeded to transplant a median of 89 days (56-93) after diagnosis. No pts who have proceeded to transplant have relapsed, a median of 340 days (136-444) after transplant. 7/8 remain alive, 345 days (91-586) after enrolling. Conclusions: At the stage 1 interim analysis, the CR rate for ven+aza remains >60% in adverse risk younger patients. With small numbers, up-front treatment with ven+aza allows some younger pts with adverse risk disease a non IC opportunity to achieve a response and proceed to transplant; most of those who relapsed or were refractory were salvaged with IC. Download : Download high-res image (229KB) Download : Download full-size image Disclosures Pollyea: Syndax: Consultancy; Syros: Consultancy; Abbvie: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; Karyopharm: Consultancy; Novartis: Consultancy; Genentech: Consultancy; Amgen: Consultancy; 47: Consultancy, Research Funding; Janssen: Consultancy; Agios: Consultancy; Glycomimetics: Other; Celgene/BMS: Consultancy; Pfizer: Consultancy; Takeda: Consultancy. OffLabel Disclosure: Venetoclax for younger patients fit for induction chemotherapy