New Therapeutic Strategies for Mantle Cell Lymphoma

Mantle cell lymphoma (MCL) is a rare (2-6%) and an aggressive form of B-cell lymphoma that is characterized by overexpression of cyclin D1 caused by the t(11;14)(q13;q32) translocation. MCL typically presents predominantly in males and a median age at diagnosis of 65 to 70 years. MCL remains essentially incurable with conventional chemotherapy and prognosis remains poor in spite of recent advances in treatment. For the young fit patients, an intensive approach, which consist of an immune-chemotherapy containing high-dose cytarabine followed by high-dose chemotherapy with autologous stem cell transplantation (autoSCT), has been demonstrated to induce higher response and survival rates. Recently, rituximab (R) maintenance following autoSCT improves survival. R-hyper-CVAD/MA (R in combination with hyper-fractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone alternating with high-dose methotrexate/cytarabine) also showed high response and survival rates in phase II trial although therapy-associated toxicities hamper its feasibility. For the elderly patients, the majority is not feasible for dose-intensified regimens. R-CHOP (R, cyclophosphamide, doxorubicin, vincristine, prednisone) with R maintenance, bendamustine-R and a combination with bortezomib, VR-CAP (bortezomib, R, cyclophosphamide, doxorubicin, and prednisone), is considered as the first-line standard chemotherapy. For relapsed patients, in addition to a conventional salvage therapies, a new targeted therapy should be considered. Ibrutinib achieves the highest response rates and, in some cases, long-term remissions. Other small molecules, such as immunomodulatory (lenalidomide), Bruton's tyrosine kinase (BTK) inhibitor (acalabrutinib), BCL-2 inhibitor (venetoclax) and phosphatidylinositol 3-kinase (PI3K) inhibitor (idelalisib, copanlisib), are evaluating. In this symposium, new therapeutic strategies incorporating newer targeting drugs for MCL will be discussed.