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

To improve the tolerability of posttransplant 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. (Ven) with FluBu2 (fludarabine/busulfan) reduced-intensity chemotherapy chemotherapy: (kee-moe-THER-uh-pee) The use of medicines that kill cells (cytotoxic agents). People with high-risk or intermediate-2 risk myelodysplastic syndrome (MDS) may be given chemotherapy to kill bone marrow cells that have an abnormal size, shape, or look. Chemotherapy hurts healthy cells along with… transplantation using 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 graft-versus-host disease (GVHD) graft-versus-host disease (GVHD): Also called GVHD, it is a common complication of bone marrow/stem cell transplantation. It is caused when the donor's immune cells, now in the patient, begin to see the the patient's body as foreign and mount an immune response. GVHD most commonly effects the recipient's skin, intestines, or liver… prophylaxis, followed by all-oral Ven/decitabine-cedazuridine (Ven/Dec-c) maintenance in patients with poor-risk MDS/AML (myelodysplastic syndrome/acute myeloid leukemia; N = 30). Overall, 58% had previous Ven exposure and 63% had TP53 mutation mutation: Any change or alteration in a gene. A mutation may cause disease or may be a normal variation. Paroxysmal nocturnal hemoglobinuria (PNH) occurs because of a mutation in the PIG-A gene of a single stem cell in the bone marrow. ; 15/19 had TP53 multihit state. At a median of +55 days, prophylactic prophylactic: Something that prevents or protects. Blood thinners may be given as a prophylactic to prevent blood clots in high risk patients. maintenance therapy with Ven (400 mg on days 1-14) and Dec-c (35 mg decitabine decitabine: It works by reducing the amount of methylation in the body. Methylation is a process that acts like a switch to turn off or “silence” genes in certain cells. When these genes (called tumor suppressor genes) are turned off, MDS cells and cancer cells can grow freely. Decitabine is approved by the U… and 100 mg cedazuridine tablet on days 1, 3, and 5, or days 1, 2, and 3) was initiated for 8 cycles of 42 days each in 26 of 30 patients (87%; of the remaining patients, 3 relapsed early and 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 although infections were rare (n = 2). No dose-limiting toxicities occurred. The 6-month acute GVHD grade 2 to 4 rate was 13%. The 1-year moderate/severe chronic GVHD rate was 31%. At a median follow-up of 25.1 months (range, 15-33), median overall survival (OS) and progression-free survival (PFS) were not reached. On maintenance, 2-year OS was 77%, PFS was 62%, nonrelapse mortality was 0%, and cumulative incidence of relapse was 38%. Exploratory studies identified 96% of patients had pretransplant next-generation sequencing molecular residual disease (MRD) positivity, favorable survival in those with non-TP53 MRD positivity, and delayed conversion on maintenance in 11 of 18 (61%) with TP53-MRD positivity. Patient-reported outcomes assessed in the first 6 months of maintenance were stable except for emotional function, which significantly improved. This trial was registered at www.ClinicalTrials.gov as NCT03613532.