Update on the molecular pathogenesis and clinical treatment of Mantle Cell Lymphoma (MCL): minutes of the 9th European MCL Network conference.

摘要

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.