Mantle Cell Lymphoma – Cutting- edge Diagnostics and Treatment Approaches

Abstract

Mantle cell lymphoma represents a specific subtype of B -cell non-Hodgkin lymphoma characterized on the molecular level by translocation t(11;14)(q13;q32) leading to aberrant overexpression of cyclin D1 and deregulation of the cell cycle. Despite sporadic indolent forms of mantle cell lymphoma, majority of patients present with advanced aggressive disease that requires immediate treatment. Despite chemosensitive nature of mantle cell lymphoma, approximately 10% patients present with a refractory disease, and the vast majority of patients who initially respond to therapy, relapse sooner or later. The course of mantle cell lymphoma thus represents a chronically relapsing malignancy requiring further and further lines of therapies. Prognosis of relapsed or refractory (R/ R) mantle cell lymphoma is dismal. The goal of this article is to provide a cutting -edge review of currently used diagnostic and treatment approaches for mantle cell lymphoma. Several key modifications of the therapeutic algorithm of mantle cell lymphoma treatment implemented in the past 10 years resulted in significantly improved prognosis of patients. The milestones in the therapy of mantle cell lymphoma include incorporation of anti-CD20 monoclonal antibody rituximab into induction therapy, intensification of polychemotherapeutic regimen including implementation of high-dose cytarabine, consolidation of response with high-dose therapy and autologous stem cell transplantation (HDT ASCT) in younger fit patients, and maintenance therapy with rituximab in the elderly patients. Besides such "optimization" of frontline therapy, introduction of novel antilymphoma agents into therapy of R/ R mantle cell lymphoma also contributed (and will contribute in the future) to improved prognosis of mantle cell lymphoma. Among these agents, there is a new cytostatic drug bendamustine, Bruton tyrosine- kinase inhibitor ibrutinib, immunomodulatory agent lenalidomide, mTOR inhibitor temsirolimus and proteasome inhibitor bortezomib. The overall survival of mantle cell lymphoma virtually doubled in the recent 10 years as a result of two key factors: 1. optimization of frontline therapy with "conventional" antilymphoma agents, and 2. brand new possibilities of therapy for R/ R mantle cell lymphoma thanks to the introduction of novel antilymphoma agents. Combinatorial approaches using most efficacious combinations of novel and "conventional" anti-mantle cell lymphoma agents will definitely lead to further improvements of survival parameters in mantle cell lymphoma patients in near future.