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More is better: Combination therapies for myelodysplastic syndromes

PubMed Abstract: 
Original Publication Date: 
Tuesday, April 7, 2015

Research Review:

The myelodysplastic syndromes are a bone marrow failure disorder characterized by ineffective maturation of cells, low blood counts, and risk of transformation to acute myeloid leukemia (AML).  There are currently three FDA-approved medications for MDS: lenalidomide, azacitidine, and decitabine.  Although these agents can be effective in the treatment of MDS, none are curative.  Much of the current research in the field focuses on combining these active agents with other classes of drugs in the hopes of better efficacy without sacrificing safety.


-Combination therapy can have multiple advantages over single agent therapy in MDS, including potential additive effects of two agents, targeting more than one pathway involved in disease progression, and using lower doses of individual agents to minimize side-effects.

-One method of combination therapy is using an epigenetic approach, where one combines azacitidine or decitabine (the class of drugs known as hypomethylating agents) with a class of drugs labeled histone deacetylase inhibitors.  Several trials have shown promising results with increase in response rates and acceptable side-effect profiles.

-Azacitidine and lenalidomide, two FDA approved drugs in MDS, have also been combined with promising results in the higher-risk MDS population, possibly due to synergistic effects since they target different pathways.

-Lenalidomide has also been used in combination with other drugs, such as ezatiostat hydrochloride and epoeitin alpha in lower-risk MDS patients in an effort to reduce red blood cell transfusion dependence.

-The current FDA approved agents have been tested with platelet boosting agents, such as romiplostim, in an effort to increase platelet counts and decrease clinically significant bleeding.

-Other mechanisms, such as immunosuppression and proteasome inhibition, are also being examined as possible strategies for MDS patients.  This includes the use of agents such as etanercept and bortezomib.


-Combination therapy has many potential benefits in MDS, including the additive benefit of more than one agent and the reduction of side effects by using lower doses of individual medications.

-Several trials are now underway to test combinations of agents in MDS in order to determine the optimal dose, schedule, and efficacy.

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