Immunotherapy in mantle cell lymphoma: anti-CD20-based therapy and beyond

Mantle cell lymphoma (MCL), an aggressive non-Hodgkin's lymphoma characterized by t(11; 14)(q13; q32) chromosomal translocation and overexpression of cyclin D1, has the worst prognosis among all lymphomas. Recent advances in biology, genetics, and immunology have supported the development of immunotherapy in MCL. Rituximab monotherapy in MCL has limited activity. It is more effective when used in combination with chemotherapy such as R-CHOP, R-hyperCVAD/MTX-Ara-C, or R-FCM as front-line or salvage therapy for mantle cell lymphoma. Maintenance with Rituximab was shown to prolong response duration. Although most results have suggested that combining autologous stem cell transplantation with Rituximab may lead to durable remission, the sample size was not sufficient to declare survival benefit. Anti-CD20 radioimmunoconjugates (RICs) (90)Yttrium-ibritumomab tiuxetan and (131)Iodine-tositumomab have been used in mantle cell lymphoma even when patients are relatively resistant to Rituximab-based therapy. Allogeneic stem cell transplantation is a treatment modality in advanced or relapsed MCL, particularly using reduced-intensity conditioning. MCL may have high response rates and sustained remissions after donor lymphocyte infusion. Dendritic cells (DCs) fused with MCL cells for immunostimulation have preliminarily shown anti-lymphoma effects as well. Idiotype vaccination in MCL patients following Rituximab-containing chemotherapy induced tumor-specific T-cell immunity in the absence of B cells. Other immunotherapy, such as the combination of thalidomide with Rituximab, has shown substantial antitumor activity. A Phase I/II study is ongoing to determine the maximum tolerated dose (MTD) and the efficacy of lenalidomide in combination with Rituximab for relapsed/refractory MCL. This review summarizes the latest and exciting advances in MCL.