Unmet needs in the treatment of mantle cell lymphoma.

Mantle cell lymphoma is one of the most challenging hematologic malignancies, owing to an aggressive disease course, a high rate of relapse, and lack of standard of care. In the United States, mantle cell lymphoma accounts for approximately 6% of all newly diagnosed cases of non-Hodgkin lymphoma. Because most patients are initially diagnosed with advanced-stage disease, they are often symptomatic at presentation. Common features include widespread lymphadenopathy and splenomegaly, as well as bone marrow infiltration. Leukemic involvement is found in 20% to 30% of patients. The disease course can be highly variable. Some patients may have very aggressive disease, whereas others may have a much more indolent course. The optimal frontline therapy remains undefined. Strategies include chemotherapy, immunotherapy, radioimmunotherapy, stem cell transplantation, and novel biologic agents. Although mantle cell lymphoma often responds well to frontline chemotherapy, the responses are not durable and often of relatively short duration. Effective treatment options in the frontline setting have included the addition of rituximab to bendamustine. Once mantle cell lymphoma has entered the relapsed/refractory stage, it becomes more difficult to treat. Bortezomib and lenalidomide are approved for treatment of relapsed/refractory mantle cell lymphoma. The novel Bruton’s tyrosine kinase inhibitor ibrutinib appears to be highly active in relapsed/refractory mantle cell lymphoma. Other agents in clinical trials include cladribine, idelalisib, and IPI-145.