The role of targeted treatment in mantle cell lymphoma: is transplant dead or alive?

Abstract

Based on the profound biological insights of the last years into the molecular pathogenesis of mantle cell lymphoma and the clinical introduction of new targeted drugs, with high efficacy and a good safety profile, the therapeutic scenario for this tumor has been shown to be thoroughly favourable. No longer characterized by a uniformly dismal prognosis, mantle cell lymphoma has been revealed as a spectrum of different diseases, ranging from very indolent cases to highly aggressive and refractory ones. Thus, there is an urgent need to adapt therapy to accommodate the diverse presentations of the disease. High-dose chemotherapy, followed by autologous stem cell transplantation is the current standard of care for younger patients, generally providing high responses and long survival rates, but hampered by acute and long-term toxicity. In addition, some patients may be overtreated, while others could benefit from targeted approaches, based on the new, molecular-directed compounds. Such a personalized treatment based on the specific characteristics of individual patients may be guided by validated prognostic tools, such as the Mantle Cell Lymphoma International Prognostic Index and the Ki-67 Proliferative Index, as well as by early predictors of treatment response, like minimal residual disease analysis. Moreover, mutation screening of distinctive genomic alterations may provide new, predictive biomarkers, with an additional impact on clinical practice. Only after tailoring treatment according to the clinical and biological heterogeneity of the disease the role of transplantation and modern therapeutic options will be redefined in mantle cell lymphoma.