New Strategies in the Treatment of Mantle Cell Lymphoma

Abstract

Mantle cell lymphoma (MCL) is a rare type of non-Hodgkin lymphoma that traditionally has been thought to possess the poor-risk features of both indolent lymphoma, with its incurability, and aggressive lymphoma, with its ability to proliferate rapidly. Although there is considerable debate as to whether MCL can be cured, a number of retrospective studies are beginning to suggest an improvement in overall survival over the past decade, likely coinciding with the introduction of rituximab, more intensive chemotherapy, and the increasing use of autologous stem cell transplant (ASCT) in first remission. At present, intensive induction chemotherapy regimens consistently produce a response rate of >90%, sometimes even 100% in the first-line setting, and consolidation with ASCT in first remission can improve the complete response rate to 90%. The emergence of a more sophisticated understanding of the underlying pathogenesis, coupled with a host of new agents and targets, has again created new opportunities to improve the care of our patients with MCL. Here, we discuss many of these developments and how they may potentially affect the natural history of this disease. Clin Cancer Res; 18(13); 3499-508. Ó2012 AACR.

Synergistic anti-tumor activity of acadesine (AICAR) in combination with the anti-CD20 monoclonal antibody rituximab in in vivo and in vitro models of mantle cell lymphoma

“…The clinical course of MCL is characterized by an initial high response rate but a constant relapse pattern, resulting in a poor long-term outcome [2]. It has been reported that first-line chemotherapy including rituximab is associated with significantly improved survival in older patients diagnosed with MCL compared with chemotherapy alone [3].…”

“…It has been reported that first-line chemotherapy including rituximab is associated with significantly improved survival in older patients diagnosed with MCL compared with chemotherapy alone [3]. In the last years, the proteasome inhibitor bortezomib and bendamustine, an hybrid drug between a nucleoside analog and an alkylating agent, have been approved in USA for the treatment of patients with relapsed MCL patients, either alone or in combination with rituximab [2]. Here, we observed an antagonistic effect between bortezomib and acadesine whereas for bendamustine we detected an additive or synergistic effect depending on the MCL cell line.…”

“…In addition, other mechanisms such as activation of cell survival pathways are integrated to drive MCL pathogenesis. Current frontline combination chemotherapies and intensive chemoimmunotherapy followed by stem-cell transplantation have improved the outcome for patients with this disease [2]. Although these regimens have high initial response rates, most patients relapse and die from disease-related complications [1].…”

“…The introduction of rituximab, a chimeric mouse anti-human CD20 monoclonal antibody, has shown improvement of response rates when used in combination with standard chemotherapy [3;4]. In the last years, new strategies that target crucial biological pathways such as ubiquitin-proteasome system, mTOR pathway and BCR signaling have been developed [2;5;6]. In particular, recently it has been described that Ibrutinib, a BTK inhibitor shows durable single-agent efficacy in relapsed or refractory MCL [7].…”

Durable Remission of Mantle Cell Lymphoma Relapsing a Third Time After Allogeneic Hematopoietic Stem Cell Transplantation Treated With Rituximab, Bortezomib, Donor Lymphocytes, and Pegylated Interferon

“…2,3 Given the lower risk of causing transplant-related mortality, most centers prefer to use a reduced-intensity conditioning approach because cures after allogeneic transplantation occur not as a consequence of dose-intensive conditioning but rather are mediated by engrafting donor T cells that induce powerful and curative GVT effects. 3,5,9 Investigators recently reported excellent results after reduced-intensity transplants for relapsed MCL. By using a novel reduced-intensity regimen, Khouri et al 10 reported a 100-day mortality of 0%, a CR rate of 94%, a 3-year progression-free survival of 82%, and a median overall survival of 85% in patients with advanced/ recurrent MCL.…”