Management of relapsed and refractory mantle cell lymphoma: a review of current evidence and future directions for research

Mantle cell lymphoma (MCL) is an uncommon subtype of non-Hodgkin’s lymphoma (NHL) with heterogeneous disease biology and a high response rate to initial therapy. While duration of response (DOR) to frontline treatment has improved with advances in therapy, including the use of intensified cytarabine containing induction regimens and autologous stem cell transplantation (ASCT) consolidation, MCL remains incurable with standard therapy. Relapsed MCL typically follows an aggressive clinical course. Management is challenging and depends upon patient characteristics, preferences, and candidacy for al-logeneic hematopoietic cell transplant (allo-HCT). Chemo-immunotherapy, including cy-tarabine and bendamustine containing regimens, remain an important option both for salvage therapy prior to allo-HCT and for disease control for patients not eligible for transplant. The biologic agents bortezomib, lenalidomide, and ibrutinib are approved as single agent therapy for relapsed or refractory MCL and provide effective treatment options including in older patients. While ibrutinib represents a therapeutic breakthrough in the relapsed setting, patients will eventually progress and outcomes are poor following pro-gression, leaving a need for novel treatments. In this review we will review in detail the management of relapsed and refractory MCL and discuss future directions under investi-gation including new targeted biologic agents, novel combination therapies, and adoptive immunotherapy.