Risk-Adapted, Individualized Treatment Strategies of Myelodysplastic Syndromes (MDS) and Chronic Myelomonocytic Leukemia (CMML).

Abstract

Simple SummaryMyelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) are two blood cancers with variable symptoms of low blood counts (fatigue, bleeding, infection risk) and risk of progression to acute myeloid leukemia. Management decisions should be guided by individual patient and disease characteristics and based on validated risk stratification tools. Supportive care with red blood cell transfusions and medications to stimulate blood cell production remains the mainstay of therapy for lower-risk MDS and CMML patients. For higher-risk patients, a bone marrow transplant is the only potentially curative option, but most patients are not candidates for this intensive therapy. In this case, the hypomethylating agents (HMA) azacitidine and decitabine are standard of care. However, response rates to HMA are low and responses are only transient highlighting the need for novel approaches. While an oral version of decitabine has been recently approved, several targeted therapies are in development, but none has been approved to date.Myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) are two distinct blood cancers with a variable clinical symptom burden and risk of progression to acute myeloid leukemia. Management decisions should be guided by individual patient and disease characteristics and based on validated risk stratification tools. While supportive care with red blood cell transfusions, erythropoiesis-stimulating agents, and iron chelation remains the mainstay of therapy for lower-risk (LR)-MDS patients, luspatercept has recently been approved for transfusion-dependent anemic LR-MDS patients ending a decade without any new drug approvals for MDS. For higher-risk patients, allogeneic hematopoietic cell transplant (allo-HCT) remains the only curative therapy for both MDS and CMML but most patients are not eligible for allo-HCT. For those patients, the hypomethylating agents (HMA) azacitidine and decitabine remain standard of care with azacitidine being the only agent that has shown an overall survival benefit in randomized trials. Although early results from novel molecularly driven agents such as IDH1/2 inhibitors, venetoclax, magrolimab, and APR-246 for MDS as well as tagraxofusp, tipifarnib, and lenzilumab for CMML appear encouraging, confirmatory randomized trials must be completed to fully assess their safety and efficacy prior to routine clinical use. Herein, we review the current management of MDS and CMML and conclude with a critical appraisal of novel therapies and general trends in this field.