title: Update on the molecular pathogenesis and clinical treatment of Mantle Cell Lymphoma (MCL): minutes of the 9th European MCL Network conference.
abstract: Mantle cell lymphoma (MCL) is a distinct subtype of malignant lymphoma which is characterized by the chromosomal translocation t(11;14)(q13;q32), resulting in constitutional overexpression of cyclin D1 and cell cycle dysregulation in virtually all cases. Clinically, MCL shows an aggressive clinical course with a continuous relapse pattern and a median survival of only 3-5 years. However, recently a subset of 15% long-term survivors has been identified with a rather indolent clinical course, even after conventional treatment strategies only. Advanced stage disease is usually apparent already at first clinical manifestation; thus, conventional chemotherapy is only palliative, and the median duration of remissions is only 1-2 years. Emerging strategies including proteasome inhibitors, immune modulatory drugs (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 remain a challenge. In 2000 the European MCL Network ( http://www.european-mcl.net ) was founded, consisting of 15 national lymphoma study groups supplemented by experts in histopathology and molecular genetics. During the past decade, the European consortium has successfully initiated the largest phase III trials in MCL worldwide, with a current annual recruitment of almost 200 patients per year in first-line studies. In detail, in prospective randomized studies, the addition of a B-lymphocyte specific antibody doubled the median progression-free survival from 14 to 28 months, and a dose-intensified consolidation with high-dose radiochemotherapy and subsequent autologous stem cell transplant resulted in superior response duration (3.7 vs. 1.6 years) and even improved overall survival in a recent analysis. Future strategies will apply individualized approaches according to the molecular risk profile of the patient. At the recent annual conference in Jerusalem, recent results of molecular pathogenesis, analyses of current clinical trials, and new study concepts were discussed.
authors.affiliation: Department of Medicine III, University Hospital Grosshadern/LMU Munich, Munich, Germany. Martin.Dreyling@med.uni-muenchen.de
authors.forename: Martin
authors.initials: M
authors.lastname: Dreyling
authors.forename: Eva
authors.initials: E
authors.lastname: Hoster
authors.forename: Silvia
authors.initials: S
authors.lastname: Bea
authors.forename: Elena
authors.initials: E
authors.lastname: Hartmann
authors.forename: Heike
authors.initials: H
authors.lastname: Horn
authors.forename: Grit
authors.initials: G
authors.lastname: Hutter
authors.forename: Itziar
authors.initials: I
authors.lastname: Salaverria
authors.forename: Christiane
authors.initials: C
authors.lastname: Pott
authors.forename: Marek
authors.initials: M
authors.lastname: Trneny
authors.forename: Steven
authors.initials: S
authors.lastname: Le Gouill
authors.forename: Sergio
authors.initials: S
authors.lastname: Cortelazzo
authors.forename: Michal
authors.initials: M
authors.lastname: Szymczyk
authors.forename: Wojciech
authors.initials: W
authors.lastname: Jurczak
authors.forename: Ofer
authors.initials: O
authors.lastname: Shpilberg
authors.forename: Vincent
authors.initials: V
authors.lastname: Ribrag
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D003226:Congresses as Topic; D006801:Humans; D020522:Lymphoma, Mantle-Cell / Q000209:etiology* / Q000628:therapy*; D033581:Stem Cell Transplantation