Current and Emerging Therapies in Mantle Cell Lymphoma

L. Kyle Brett, Michael E. Williams

Mantle Cell Lymphoma, characterized by the t(11;14)(q13; q32) chromosomal translocation and cyclin D1 expression, remains one of the most challenging lymphoma subtypes to treat. Therapy can be divided into treatment modalities for younger, stem cell transplant (SCT)-eligible patients vs older, SCT-ineligible patients. For clinically fit patients younger than 60-65 years of age we recommend cytarabine-containing induction and conditioning regimens such as Rituximab (R)-CHOP alternating with R-DHAP followed by autologous SCT consolidation. Elderly patients benefit from R-bendamustine or R-CHOP with maintenance rituximab following induction therapy, especially after R-CHOP. While standard chemoimmunotherapy provides high overall response rates, the responses are not durable and sequential therapies are thus necessary. MCL is proving to be sensitive to novel therapies that may in the near future become useful adjuncts to standard regimens. For example, bortezomib, lenalidomide, and temsirolimus each have single-agent efficacy in relapsed and refractory disease. Several targeted agents are emerging that likewise may transform management of MCL. The B-cell receptor pathway appears to be critical in the pathogenesis of MCL, and novel agents such as ibrutinib and idelalisib that target this signaling pathway are highly active in relapsed and refractory MCL. Similarly, cell cycle inhibitors targeting cyclin dependent kinases as well as HDAC inhibitors have shown promise in early studies.