Venetoclax and Hypomethylating Agents (HMAs) Induce High Response Rates in MDS, Including Patients After HMA Therapy Failure

Hypomethylating agents (HMAs) are the current standard of care in high-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… (MDS). However, only ∼50% of patients with MDS respond to HMAs and most responding patients eventually progress.1,2  Outcomes after HMA failure are particularly poor, with a median overall survival (OS) of 4 to 6 months.3,4   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. is an oral selective inhibitor of the anti-apoptotic protein BCL-2 and, in combination 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… , increased responses and prolonged survival when compared with azacitidine alone in a phase 3 study for patients with previously-untreated acute myeloid leukemia acute myeloid leukemia: (uh-KYOOT my-uh-LOYD loo-KEE-mee-uh) A cancer of the blood cells. It happens when very young white blood cells (blasts) in the bone marrow fail to mature. The blast cells stay in the bone marrow and become to numerous. This slows production of red blood cells and platelets. Some cases of MDS become… (AML), ineligible for intensive 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… .5  Preclinical studies have demonstrated that BCL-2 is overexpressed in high-risk MDS, and BCL-2 inhibition induces apoptosis apoptosis: Programmed cell death. in MDS progenitor cells.6,7  However, MDS is defined by bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. dysplasia and cytopenias, and the addition of venetoclax to HMAs in MDS has potential for cumulative myelosuppression. Phase 1 studies evaluating venetoclax in combination with HMAs in treatment-naïve and relapsed/refractory (R/R) MDS are currently under investigation.8,9  Here, we present real-world evidence supporting the use of venetoclax in combination with HMAs in patients with MDS. We also identify risk factors impacting response and survival after treatment with the combination.