Introduction: 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… /neoplasms (MDS) comprise a heterogeneous group of clonal myeloid malignancies characterized by ineffective hematopoiesis hematopoiesis: (hi-mat-uh-poy-EE-suss) The process of making blood cells in the bone marrow. and a variably increased 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). Higher-risk MDS, as defined by the revised- and molecular International Prognostic Scoring System International Prognostic Scoring System: A system that turns patient data into a score. The score tells how quickly a myelodysplastic syndrome (MDS) case is progressing and helps predict what may happen with the patient's MDS in the future. Also called IPSS. , remains largely incurable except through allogeneic hematopoietic stem cell transplantation. Management continues to rely primarily on hypomethylating agents, which were approved nearly two decades ago and remain the cornerstone of therapy despite their modest efficacy.
Areas covered: Advances in molecular profiling and next-generation sequencing have greatly improved disease classification and prognostication tools. However, with the exception of 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). , targeted therapies in higher-risk MDS remain the exception to the rule. Although numerous early-phase clinical trials clinical trials: Clinical research is at the heart of all medical advances, identifying new ways to prevent, detect or treat disease. If you have a bone marrow failure disease, you may want to consider taking part in a clinical trial, also called a research study. Understanding Clinical Trials Clinical… have yielded promising signals, phase III trials have repeatedly failed to replicate these findings. This largely reflects the intrinsic biological complexity and heterogeneity of MDS, as well as logistical challenges in trial design and execution.
Expert opinion: Examining the history and evolution of investigational pharmacotherapy in higher-risk MDS may help identify where efforts to translate early phase successes into successful phase III trials have faltered. The expanding biological knowledge base and the design of better therapies will hopefully pave the way for future therapeutic breakthroughs.
Keywords: Higher-risk MDS; cell therapy; clinical trials; hypomethylating agents; targeted therapy.