Investigational histone deacetylase inhibitors for non-Hodgkin lymphomas

Histone deacetylase inhibitors (HDIs) have been shown effective as single agents for cutaneous T-cell lymphomas, peripheral T-cell lymphomas, and B-cell lymphomas, such as follicular lymphoma and mantle cell lymphoma. Of interest, HDIs in combination with other drugs can be a treatment for Epstein-Barr virus-associated lymphoproliferative disorders. Our data of gene expression profiles in PBMCs of responders to vorinostat was discussed.

This review summarizes recent clinical trials of HDIs in non-Hodgkin lymphomas, the effects of HDIs in in vitro and mouse models, and the possibility of future combination treatments.

The HDI dosing schedule is crucial to optimize outcomes and avoid irreversible adverse effects. Responses to HDIs are slow, highlighting the need to continue treatment until the maximum response is achieved. HDIs cause hyperacetylation of histone and nonhistone proteins, resulting in various effects on neoplastic cells and immune responses in their microenvironment.

Even though HDIs are not potent as single agents, they are likely to provide promising therapeutic options when combined with other agents, i.e., BCL2/BCL-XL antagonists and proteasome inhibitors. Future studies should seek to identify biomarkers that predict patient responses to HDIs.