Current treatment standards and emerging strategies in mantle cell lymphoma.

Abstract

Mantle cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin lymphomas characterized by the chromosomal translocation t(11;14)(q13;q32) and nuclear cyclin D1 overexpression in the vast majority of cases. Most patients present with advanced stage disease, often with extranodal dissemination, and pursue an aggressive clinical course in the majority of cases. Recent improvement has been achieved by the successful introduction of monoclonal antibodies and dose-intensified approaches including autologous stem cell transplantation (ASCT) strategies. With the exception of allogeneic hematopoietic stem cell transplantation, current treatment approaches are non-curative and the corresponding survival curves are characterized by a delayed, but continuous decline and a median survival of 4 to 6 years. However, recently a subset (15%) of long-term survivors have been identified with a rather indolent clinical course even after conventional treatment strategies only. Emerging strategies such as proteasome inhibitors, IMIDs, mTOR inhibitors and others are based on the dysregulated control of cell cycle machinery and impaired apoptotic pathways. Monotherapy of these compounds achieves efficacy comparable to conventional chemotherapy in relapsed MCL, and combination strategies are currently being investigated in numerous trials; however, their introduction into clinical practice and current treatment algorithms remains a challenge.