Approaches to the management of relapsed/refractory mantle cell lymphoma: navigating an increasingly complex therapeutic landscape

INTRODUCTION: Mantle cell lymphoma (MCL) represents a distinct subtype of mature B-cell lymphoma, considered incurable with a pattern of recurrent relapses and suboptimal responses to subsequent therapies that portend poorer prognosis with each recrudescent disease. AREAS COVERED: Covalent and non-covalent Bruton tyrosine kinase inhibitors (BTKi) have transformed the therapeutic landscape of relapsed/refractory (R/R) MCL as monotherapies though these drug classes may emerge to be more effective as combinations with B-cell lymphoma-2 (BCL-2) inhibitors and immunotherapy. Immune-leveraging therapies, including chimeric antigen receptor (CAR) T-cell therapy and T-cell engaging antibodies, are gaining momentum, with the former demonstrating durable responses in a subset of patients, while the latter being evaluated in various combination regimens. Allogeneic hematopoietic stem cell transplants remain a potentially curative option for selected patients. EXPERT OPINION: This review seeks to navigate this increasingly complex therapeutic landscape while providing a suggested treatment and sequencing algorithm that may be tailored to individual patients.