Bortezomib for the treatment of mantle cell lymphoma

Introduction: Mantle cell lymphoma (MCL) is an infrequent lymphoma subtype characterized by aberrant cyclin D1 expression. As MCL is incurable, patients are destined to relapse. While there is no universally accepted treatment approach for relapsed MCL, several agents are now approved in this setting. Areas covered: Here we not only focus on the first approved agent bortezomib, but also discuss more recently approved agents as well. FDA approval in 2006 of bortezomib for patients with previously treated MCL was based on the PINNACLE study, with 33% response rate. In 2013, lenalidomide received FDA approval for MCL patients who had progressed after prior treatment that included bortezomib, based on the pivotal Phase II EMERGE study with 28% response rate. Also in 2013, the FDA granted accelerated approval of ibrutinib for patients with at least one prior therapy for MCL based on a Phase II study with 68% response rate. In Europe, temsirolimus is approved for relapsed MCL based on a randomized Phase III three-arm trial in which the higher dose of temsirolimus yielded response rate of 22%. Expert opinion: While single-agent bortezomib has activity in relapsed MCL, bortezomib in combination with immunochemotherapy are promising as initial therapy. Rational development of novel combinations will involve agents targeting other intracellular signaling pathways, epigenetic modulators and proapoptotic agents.