Dose-intense treatment of mantle cell lymphoma: can durable remission be achieved?

Mantle cell lymphoma is a distinct subtype of malignant lymphoma, which displays an aggressive clinical course with a continuous relapse pattern and the worst long-term outcome of all B-cell lymphoma. Conventional-dosed chemotherapy achieves only temporary responses with a median duration of remissions of only 1-2 years.

Addition of monoclonal antibodies has improved initial response but duration of response remained almost uninfluenced. In contrast, dose-intensified regimens including addition of high-dose Ara-C or myeloablative consolidation achieved significantly improved progression-free survival rates whereas the improvement of overall survival has not yet been definitely proven by recent multicenter trials. Various phase II studies suggest that further intensification (HyperCVAD followed by autologous stem cell transplantation) may be beneficial if tolerated. However, potentially improved efficacy has to be balanced against increased toxicity and feasibility of this approach.

Dose-intensified approaches, either cyclophosphamide, hydroxydaunorubicin (adriamycin), oncovin (vincristine), and prednisone (CHOP) +/- high-dose Ara-C followed by autologous stem cell transplantation or HyperCVAD with the addition of rituximab remain the current standard approach in younger patients up to 65 years. Future strategies will focus in a slightly different direction, namely to integrate the increasing number of molecular targeted compounds (proteasome inhibitors, mammalian target of rapamycin antagonists or immunomodulatory drugs like lenalidomide) into multimodal approaches to overcome the still disappointing long-term prognosis of mantle cell lymphoma.