Mantle Cell Lymphoma: the Role of Risk-Adapted Therapy and Treatment of Relapsed Disease

In this review, the current treatment strategies are recapped, evolving agents are discussed, and we provide guidance in treating R/R MCL.

There has been an advancement in treatment using targeted therapy, cellular therapies including chimeric antigen receptor (CAR) T cell therapy and hematopoietic stem cell transplantation (HSCT) and novel therapeutic agents including non-covalent BTKis, bispecific antibodies, and antibody-drug conjugates for treatment of refractory and relapsed mantle cell lymphoma. Mantle cell lymphoma (MCL) is a mature B-cell lymphoma that is associated with a poor prognosis. Current treatments include immunochemotherapy, chemotherapy and autologous stem cell transplantation (SCT) which place patients in remission but result in relapse. Chemoimmunotherapy uses chemotherapeutic agents paired with rituximab in patients who have chemo-sensitive disease with prolonged remission of at least > 2 years and/or have contraindications to chemotherapy that serve as bridges to more definitive treatment. Additional therapies including proteosome inhibitor-based therapies and immunomodulators, like bortezomib and lenalidomide, can be used as single agents or in combination with others. Bruton's tyrosine kinase (BTK) inhibitors including ibrutinib, acalaburtinib, and zanubrutinib have also been proven effective for the treatment of (R/R) disease. Another agent is Venetoclax, a robust drug that can be used in MCL after progression or intolerance to BTKi. Newer advances in the management of MCL have led to the utilization of cellular therapies including chimeric antigen receptor (CAR) T cell therapy and SCT that are options for healthy young (< 65 years old) who have progressed through several lines of therapies. With progression of disease, mutations are acquired that cause therapy resistance. Novel therapeutic agents such as non-covalent BTKis, bispecific antibodies, and antibody-drug conjugates are paving the way for advancements in treatment for R/R MCL. R/R MCL is a complex disease with many therapeutic options none of which has been proven superior in head-to-head comparison. In this review, the current treatment strategies are recapped, evolving agents are discussed, and we provide guidance in treating R/R MCL.