Recent advances and future directions in newly diagnosed mantle cell lymphoma

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.

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.

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.