Mantle cell lymphoma: evolving management strategies

Abstract

Mantle cell lymphoma (MCL) is a rare and aggressive form of non-Hodgkin’s lymphoma that generally affects older individuals and continues to have one of the worst outcomes of all the lymphomas. Over the last decade, there has been a widespread adoption of cytarabine-based therapy in younger patients, and the incorporation of rituximab into chemotherapeutic regimens has become an evidence-based standard of care. However MCL remains a largely incurable disease, and following relapse, it can be a challenge to manage. Although it is possible to define prognosis reliably, there are, as yet, no clear diagnostic or response-adjusted parameters that can help to guide therapeutic decisions. However, there are a number of highly active targeted therapies that are moving into the clinic that are set to transform the therapeutic paradigm for this disease in the very near future. This review will explore the molecular pathogenesis of MCL and the current and evolving therapeutic strategies for this disease.

Activity of ibrutinib in mantle cell lymphoma patients with central nervous system relapse

“…Although infrequent, it has rapidly fatal consequences with a poor median survival. 2 CNS relapse in MCL is a significant unmet medical need and its very poor prognosis with current treatment options 11 highlights the urgent need for alternative therapeutic approaches. This is the first report describing the efficacy of ibrutinib in MCL patients with CNS relapse.…”

B7-H3 silencing inhibits tumor progression of mantle cell lymphoma and enhances chemosensitivity

“…Mantle cell lymphoma (MCL), a heterogeneous subtype of B-cell non-Hodgkin lymphoma (NHL), accounts for ~7% of NHL cases in the USA and Europe and has one of the worst outcomes of all the lymphomas (1,2). It is characterized by the t(11;14) (q13;q32) translocation, which results in overexpression of cyclin D1 and deregulation of the cell cycle (2).…”

Crosstalk between ROR1 and BCR pathways defines novel treatment strategies in mantle cell lymphoma

“…1 Translocation t(11;14)(q13;q32) and the consequent overexpression of CCND1 (cyclin D1) is the key event of molecular pathogenesis of MCL, along with somatic mutations in the regulatory genes of the NF-kB pathway (10%-15%) and mutations in the TP53 gene (15%-28%). 2 Besides common chemotherapeutic drugs, targeting the B-cell antigen receptor (BCR)-signaling pathway has been shown to be effective and resulted in the approval of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib for MCL therapy.…”