Mantle cell lymphoma: from pathogenesis to treatment for 2024 and beyond

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Mantle cell lymphoma (MCL) is a rare B-cell non-Hodgkin lymphoma with diverse subtypes (cMCL, LV-MCL, ISMCN).
• Clinical presentations range from indolent to aggressive, necessitating tailored treatment strategies.
• The hallmark genetic alteration is the t(11;14) translocation, leading to CCND1-IGH gene fusion.

Purpose of the Study:

• To review the current understanding of MCL subtypes, their clinical variability, and genetic underpinnings.
• To discuss the evolving landscape of MCL treatment, including established and emerging therapeutic modalities.
• To highlight ongoing research frontiers and future directions in MCL management.

Main Methods:

• Literature review of MCL classification, pathogenesis, and treatment strategies.
• Analysis of current clinical practices and emerging therapeutic targets.
• Synthesis of data on novel agents and management of challenging MCL presentations.

Main Results:

• MCL subtypes exhibit significant differences in clinical behavior and prognosis.
• Treatment options have expanded beyond conventional chemotherapy to include targeted immunotherapies.
• Bruton's tyrosine kinase (BTK) inhibitors and CAR-T therapies are increasingly important, especially for relapsed/refractory disease.

Conclusions:

• Optimal management of MCL requires consideration of subtype, genetic features, and disease stage.
• Emerging therapies like non-covalent BTK inhibitors and bispecific antibodies show promise for improving outcomes.
• Addressing TP53-mutated MCL and central nervous system relapse remains a critical area for future research.