Everolimus in diffuse large B-cell lymphomas

Satisfactory treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is not currently available and novel therapies are needed. mTOR is an intracellular kinase that is part of an aberrantly activated pathway in DLBCL. Preclinical studies in DLBCL cell lines demonstrated that everolimus, an oral selective mTOR inhibitor, induces cell cycle arrest and is synergistic with rituximab. Phase I studies indicated 10 mg daily to be the best dosing of everolimus in DLBCL. A large Phase II study in relapsed/refractory DLBCL confirmed the substantial activity (overall response rate: 30%) and good tolerability of everolimus in DLBCL, with thrombocytopenia being the main toxicity. The combination of everolimus and rituximab showed encouraging results (objective response rate: 38%; complete response: 13%), without increasing toxicity. Combination studies of everolimus with novel agents or with immunochemotherapy are underway.