Relapsed or Refractory Mantle Cell Lymphoma: Available and Emerging Therapies

Mantle cell lymphoma (MCL) is a mature B-cell non-Hodgkin lymphoma (NHL) that accounts for 5–7% of all NHL. In most cases, it is characterized by t(11;14) leading to cyclin D1 overexpression. MCL displays a heterogeneous clinical behavior, ranging from a very indolent to a very aggressive clinical course. Biological features associated with aggressive disease include morphology (pleomorphic or blastoid), high proliferation index (Ki67 >30%), adverse clinical scores (Mantle Cell Lymphoma International Prognostic Index [MIPIb])3, and TP53 mutation status. Patients who relapse within 24 months of initial treatment (POD24) have a poor prognosis with median overall survival (OS) of approximately 12 months. Most patients achieve long-term disease control with first-line treatment, which currently involves induction rituximab-containing chemotherapy with or without autologous stem cell transplantation, followed by maintenance rituximab. Trials assessing Bruton tyrosine kinase inhibitors (BTKi) and other novel agents in the first-line setting have been recently published or are ongoing. These options are currently not available in Canada outside of clinical trials but may become standard of care in the future. Relapse after first-line therapy is inevitable, and curability outside the context of allogeneic stem cell transplant (alloSCT) remains unclear, with most patients eventually requiring second and subsequent lines of therapy. In the last decade, new therapies have changed the treatment landscape of relapsed/refractory (R/R) MCL, and their optimal sequencing or combination remain unclear. Treatment options will be described herein, with a proposed treatment algorithm for R/R MCL (Figure 1).