Efficacy and Safety of Venetoclax Plus Azacitidine for Patients With Treatment-Naive High-Risk Myelodysplastic Syndromes

Patients with higher-risk myelodysplastic syndromes myelodysplastic syndromes: (my-eh-lo-diss-PLASS-tik SIN-dromez) A group of disorders where the bone marrow does not work well, and the bone marrow cells fail to make enough healthy blood cells. Myelo refers to the bone marrow. Dysplastic means abnormal growth or development. People with MDS have low blood cell count for at… (HR MDS) have a median survival of ~1.5 years with azacitidine azacitidine: 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. Azacitidine is approved by the U… , and hematopoietic stem cell transplantation is their only curative option. Therefore, improved therapies are needed. This phase 1b study investigated safety and efficacy 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. , a selective BCL-2 inhibitor, at the recommended phase 2 dose (RP2D: 400 mg for 14 days/28-day cycle), in combination with azacitidine (75 mg/m2 for 7 days/28-day cycle) for treatment-naive HR MDS (NCT02942290). Safety was the primary outcome, and complete remission (CR) rate was the primary efficacy outcome. Secondary outcomes included rates of modified overall response (mOR), hematologic improvement (HI), overall survival (OS), and time to next treatment (TTNT). As of May 2023, 107 patients received venetoclax and azacitidine combination at the RP2D. Best response of CR or marrow CR was observed in 29.9% and 50.5% of patients (mOR, 80.4%). Median OS was 26.0 months, with 1-year and 2-year survival estimates of 71.2% and 51.3%, respectively. Of 59 patients who were red blood cell red blood cell: The most numerous type of blood cell in healthy people. Red blood cells contain hemoglobin, a protein that picks up oxygen in the lungs and brings it to cells in all parts of the body. Also called erythrocyte, RBC. and/or platelet transfusion platelet transfusion: A procedure in which platelets are given to a person through an intravenous (IV) line into the bloodstream. Platelets are more likely than red blood cells to cause an immune response, such as chills and fever. The use of platelets from one donor (apheresis) reduces the chance of reaction to… -dependent at baseline, 24 (40.7%) became transfusion-independent on study, including 11 (18.6%) who also achieved CR. Fifty-one (49.0%) of 104 evaluable patients achieved HI. Median TTNT excluding transplantation was 13.4 months. Adverse events reflected known safety profiles for venetoclax and azacitidine, including constipation (53.3%), nausea (49.5%), 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. (48.6%), thrombocytopenia thrombocytopenia: (throm-buh-sie-tuh-PEE-nee-uh) A condition in which there is a shortage of platelets in the bloodstream. This results in a low platelet count. Bleeding and bruising often occur with thrombocytopenia. (44.9%), febrile neutropenia (42.1%), and diarrhea (41.1%). Overall, venetoclax plus azacitidine at the RP2D was well tolerated and had favorable outcomes. A phase 3 study (NCT04401748) is ongoing to confirm survival benefit of this combination.