Management of higher risk myelodysplastic syndromes after hypomethylating agents failure: are we about to exit the black hole?

Management of higher risk myelodysplastic syndromes after hypomethylating agents failure: are we about to exit the black hole? Expert Rev Hematol. 2020 Sep 02;: Authors: Bewersdorf JP, Zeidan AM Abstract INTRODUCTION: Hypomethylating agents (HMA) remain the mainstay of treatment for patients with higher-risk myelodysplastic syndromes (HR-MDS). However, complete responses to HMAs are seen in <20% of cases and are typically not durable. For most patients, HMA failure is an eventual certainty which is associated with an abysmal prognosis. AREAS COVERED: PubMed and abstracts from annual meetings were searched in May 2020 to review recent studies on novel HMAs (e.g. ASTX727, CC-486, guadecitabine), molecularly targeted agents (e.g. mutant IDH1/2 inhibitors, BCL-2 inhibitors, APR246), and immune therapies (e.g. MBG453, anti-CD47) for the treatment of HR-MDS patients with HMA failure. Several molecules targeting cell signaling (e.g. rigosertib) are also in development. This manuscript also provides an overview of the state of genetic testing and its implications for an increasingly individualized treatment approach for patients with MDS. EXPERT OPINION: Advances in the understanding of the genetic and immune pathogenesis of HMA failure will lead to biomarker-driven therapeutic approaches and to an era of individualized therapeutic concepts (e.g. IDH inhibitors and APR246). The improved understanding of molecular mechanism...
Source: Expert Review of Hematology - Category: Hematology Tags: Expert Rev Hematol Source Type: research