Epigenetic Therapy Promising in Mantle Cell Lymphoma

An epigenetic/immunotherapy regimen of cladribine, Rituxan® (rituximab), and vorinostat produced a 100 percent response rate and complete remissions in 86 percent of patients with newly diagnosed mantle cell lymphoma, according to the results of a study presented at the annual meeting of the American Association of Cancer Research in Washington D.C.

Non-Hodgkin’s lymphoma (NHL) is a form of cancer that begins in the cells of the lymph system. It is characterized by the excessive accumulation of atypical (cancerous) lymphocytes. These lymphocytes can crowd the lymph system and suppress the formation and function of other immune and blood cells. Mantle cell lymphoma is a subset of NHL that accounts for approximately 2%–10% of all lymphomas. Mantle cell lymphoma is considered an aggressive form of NHL, though outcomes can vary considerably among patients.

The combination of cladribine (a purine analogue and hypomethylating agent with known epigenetic activity) and Rituxan (a targeted agent known as a monoclonal antibody) had been shown to be effective in mantle cell lymphoma. As a result of the synergistic effect of these two agents, researchers decided to add vorinostate, which is part of a class of drugs known ashistone deacetylase inhibitors.

The researchers conducted a phase II study that included 37 patients with newly diagnosed mantle cell lymphoma. The patients’ median age was 64 and 95 percent of patients had Stage IV disease. Patients received the three-drug combination every 28 days for up to six cycles. Responses were evaluated after two and six cycles. The results indicated a 100 percent overall response rate—meaning every patient experienced a response to the treatment. What’s more, 86 percent of patients experienced complete remission and 14 percent had a partial remission.

The majority of side effects were hematologic and reversible and included neutropenia, thrombocytopenia, fatigue, anorexia, and dehydration. There was one death during the study—a patient with relapsed, refractory mantle cell lymphoma with extensive pulmonary involvement, who died of pulmonary hemorrhage.

At a median follow up of 14.7 months four patients have relapsed and three have died. Of the relapsing patients, two had blastic MCL. No patient achieving a complete response has relapsed.

The researchers concluded that this combination of epigenetic and immunotherapy is nontoxic and effective in the treatment of newly diagnosed mantle cell lymphoma.


Hasanali Z, Sharma K, Spurgeon S, et al. Combined epigenetic and immunotherapy produces dramatic responses in 100% of newly diagnosed mantle cell lymphoma patients. Presented at the 2013 Annual Meeting of the American Association of Cancer Research in Washington DC, April 6-10, 2013. Abstract LB-140.

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