Myelodysplastic Syndrome with Transfusion Dependence Treated with Venetoclax

Abstract

Myelodysplastic syndromes are characterized by ineffective hematopoiesis in one or more lineages of the bone marrow. They are a group of heterogeneous clonal stem cell malignancies with a high risk to progress to acute myeloid leukemia. Currently, there are no curative FDA-approved medications for myelodysplastic syndromes. Hematopoietic cell transplantation is potentially the only curative option; however, treatment is often unavailable due to age and comorbidities. Hypomethylating agents, azacitidine and decitabine, and the immunomodulatory agent, lenalidomide, are the only FDA approved medications for the treatment of MDS, all of which are noncurative. Venetoclax, an inhibitor of the antiapoptotic protein BCL-2 used to treat chronic lymphocytic leukemia, is currently being evaluated in clinical trials as a monotherapy in high-risk myelodysplastic syndromes/acute myeloid leukemia. We present a patient with transfusion-dependent myelodysplastic syndromes refractory to the current standard of care treatment not a candidate for hematopoietic cell transplantation who responded well to monotherapy treatment with venetoclax and has since remained transfusion-independent.

Molecular Targeted Therapy and Immunotherapy for Myelodysplastic Syndrome

“…Venetoclax, approved by the FDA, is a BCL-2 inhibitor that can be used in combination with HMAs in HR-MDS patients and has been reported to have a good therapeutic response in a case study as a monotherapy (ClinicalTrials.gov (accessed on 21 September 2021) Identifier: NCT02966782) [ 204 ]. It acts as a BH3 mimetic that impedes the binding of BH3 proteins to BCL-2, hence releasing pro-apoptotic BAK and BAX proteins [ 205 , 206 ].…”