Venetoclax/FluBu2 RIC transplant followed by all-oral venetoclax/decitabine maintenance for poor risk MDS/AML

To improve the tolerability of post-transplant maintenance and outcomes despite poor risk disease genetics, we conducted a phase 1 study of venetoclax venetoclax: Venetoclax is used to treat chronic lymphocytic leukemia or small lymphocytic leukemia in adults. Venetoclax is used alone or in combination with other cancer medicines to treat these conditions. /FluBu2 RIC transplantation with tacrolimus tacrolimus: Tacrolimus is in a class of medications called immunosuppressants. It works by decreasing the activity of the immune system. Tacrolimus can be prescribed to treat and prevent graft vs host disease (GVHD). It can also be used as part of combination therapy to treat aplastic anemia in place of… /methotrexate GVHD prophylaxis followed by all-oral venetoclax/decitabine-cedazuridine (ven/dec-c) maintenance in poor-risk MDS/AML patients (N=30). 58% had prior venetoclax exposure and 63% were TP53-mutated; 15/19 had TP53 multi-hit state. At a median of +55 days, pre-emptive maintenance therapy with venetoclax (400 mg on days 1-14) and dec-c (decitabine 35 mg/cedazuridine 100 mg on days 1,3,5 or 1,2,3) was initiated for eight 42-day cycles in 26/30 (87%) patients (remaining 3 relapsed early, 1 withdrew). On maintenance, grade 3-4 neutropenia neutropenia: (noo-truh-PEE-nee-uh) A condition in which there is a shortage of neutrophils in the bloodstream. Neutrophils are a type of white blood cell. This results in a low white blood cell count. (96%) occurred though infections were rare (N=2). No DLTs occurred. 6-month acute GVHD grade II-IV rate was 13%. 1-year moderate/severe chronic GVHD rate was 31%. At a median follow up of 25.1-months (range,15-33), median OS and PFS were not reached. On maintenance, 2-year OS was 77% (95%CI,55-89), PFS 62% (95%CI,38-79), NRM 0%, and cumulative incidence of relapse 38% (95%CI,18-59). Exploratory studies identified 96% had pre-transplant NGS-MRD+, favorable survival in those with non-TP53 MRD+, and delayed conversion on maintenance in 11/18 (61%) in those with TP53 MRD+. PROs assessed in first 6-months of maintenance were stable except for emotional function, which improved (P=0.008). Trial is registered at clinicaltrials.gov/NCT03613532.