Mantle cell lymphoma: continuously improving the odds!

Introduction: Mantle cell lymphoma (MCL) responds well to initial therapy but most patients relapse and then respond only briefly to salvage therapy. Nevertheless, the median overall survival of MCL patients has dramatically improved from 30 months in the late 1970s to > 5 years at present. This is largely explained by the use of dose-intensive strategies and/or high-dose therapy upfront, and the development of novel agents for a disease that commonly shows chemoresistance in the relapse/refractory setting. Areas covered: A comprehensive review of published materials on the biology and management of MCL from the past 10 years were the focus for this review. Expert opinion: MCL outcome has definitely improved and achievement of an early deep response (complete remission [CR] or molecular CR) translates into superior survival. High-dose cytosine arabinoside -containing regimens should be used in the frontline setting in younger patients. Relapse/refractory patients still do poorly and an effort for clinical trials in that setting is essential. Three novel therapies have now been approved in MCL: two in the United States - bortezomib (proteasome inhibitor) in 2006 and lenalidomide (IMiDs) in 2013 - and one in the Europe - temsirolimus (mammalian target of rapamycin inhibitor) in 2007. A number of new compounds have shown very promising activity in MCL as well: particularly drugs targeting the B-cell receptor pathway - phosphatidylinositol 3-kinase inhibitors (idelalisib, IPI-145) and Bruton's tyrosine kinase inhibitors (ibrutinib) or pan Bcl-2 inhibitors (ABT-199). These molecules provide an opportunity to build up on the regimens used in MCL either in combination or as maintenance and will would without any doubt will revolutionize the landscape in MCL.