Recent advances and future directions in newly diagnosed mantle cell lymphoma

Introduction: There have been recent major advances in the management and treatment of mantle cell lymphoma (MCL). This uncommon subtype of mature B-cell lymphoma has a heterogeneous clinical course, including a spectrum of indolent and aggressive disease. While historically regarded as an incurable disease with a poor long-term prognosis, recent developments have improved outcomes.

Areas covered: The incorporation of targeted treatments, such as covalent Bruton’s tyrosine kinase inhibitors (cBTKi), with or without chemo-immunotherapy in the upfront treatment setting is supported by recent clinical trials indicating encouraging efficacy and safety. Measurable residual disease (MRD) testing is emerging as a potent tool in guiding treatment decision and improving outcomes while minimizing toxicities. Therapies utilized in relapsed/refractory disease, such as BCL2 inhibitors as well as immune-leveraging therapies, including T-cell engaging antibodies and chimeric antigen receptor (CAR) T-cells therapy, are being evaluated in upfront settings.

Expert opinion: This review will discuss recent advances in the upfront management of this challenging disease as well as a suggested treatment algorithm considering both availability and unavailability of first-line cBTKi. The incorporation of cBTKi to chemo-immunotherapy regimens appears effective and safe. However, patients with high-risk disease may require novel therapeutic approaches due to suboptimal outcomes with chemo-immunotherapy.