SOHO State of the Art Updates and Next Questions: An Update on Higher Risk Myelodysplastic Syndromes

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) are clonal myeloid neoplasms that cause life-limiting complications from severe cytopenias and leukemic transformation. Efforts to better classify, prognosticate, and assess therapeutic responses in HR-MDS have resulted in publication of new clinical tools in the last several years. Given limited current treatment options and suboptimal outcomes, HR-MDS stands to benefit from the study of investigational agents.Higher-risk myelodysplastic syndromes (HR-MDS) are a heterogenous group of clonal myeloid-lineage malignancies often characterized by high-risk genetic lesions, increased blood transfusion blood transfusion: A procedure in which whole blood or one of its components is given to a person through an intravenous (IV) line into the bloodstream. A red blood cell transfusion or a platelet transfuson can help some patients with low blood counts. needs, constitutional symptoms, elevated risk of progression to 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), and therapeutic need for allogeneic bone marrow bone marrow: The soft, spongy tissue inside most bones. Blood cells are formed in the bone marrow. transplantation. Use of blast percentage and other morphologic features to define myelodysplastic neoplasm subtypes is rapidly shifting to incorporate genetics, resulting in a subset of former HR-MDS patients now being considered as AML in presence of leukemia-defining genetic alterations. A proliferation of prognostic tools has further focused use of genetic features to drive decision making in clinical management. Recently, criteria to assess response of HR-MDS to therapy were revised to incorporate more clinically meaningful endpoints and better match AML response criteria. Basic science investigations have resulted in improved understanding of the relationship between MDS genetic lesions, bone marrow stromal changes, germline predispositions, and disease phenotype. However, therapeutic advances have been more limited. There has been import of the IDH1 inhibitor ivosidenib ivosidenib: A small molecule inhibitor of isocitrate dehydrogenase-1 (IDH1), which is mutated in several forms of cancer, including acute myeloid leukemia (AML). , initially approved for AML; the Bcl-2 inhibitor 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. and liposomal daunorubicin daunorubicin: Daunorubicin is in a class of medications called anthracyclines. It works by slowing or stopping the growth of cancer cells in your body. It is used in combination with other chemotherapy drugs to treat a certain type of acute myeloid leukemia (AML).  /cytarabine (CPX-351) are under active investigation as well. Unfortunately, effective treatment of TP53-mutated disease remains elusive, though preliminary evidence suggests improved outcomes with oral 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… /cedazuridine over parenteral hypomethylating agent monotherapy. Investigational agents with novel mechanisms of action may help expand the repertoire of treatment options for HR-MDS and trials continue to offer a hopeful therapeutic avenue for suitable patients.