Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphoma that is clinically characterized by its heterogeneous behavior, with courses ranging from indolent to highly aggressive cases with limited prognosis. Targeted treatment alternatives in first-line and relapse settings are more and more shaping the therapeutic landscape of MCL. The development and implementation of new targeted and immunotherapeutic approaches have already improved outcomes for patients with MCL with refractory or relapsed disease. However, long-term prognosis is still limited, and patients with relapsed/refractory (R/R) disease, especially those failing Bruton tyrosine kinase (BTK) inhibitor treatment, usually have a dismal outcome. This review summarizes the current and emerging treatment options for R/R MCL, focusing on the implementation of combined targeted treatment strategies such as BTK inhibitors and BCL2 inhibitors, as well as immune-therapeutic approaches including chimeric antigen receptor T cells and bispecific antibodies.
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