Updates on the Biological Heterogeneity of Mantle Cell Lymphoma.
Advancements in mantle cell lymphoma (MCL) have illuminated the disease's molecular diversity, leading to a wide variation in the outcomes observed in MCL. Current prognostic risk scores are continuously revised to incorporate new updates in the mechanistic or biologic understanding of MCL. Nevertheless, key high-risk features of MCL associated with rapid disease progression and poor survival, such as TP53 mutations, complex karyotypes, and blastoid or pleomorphic morphologies, remain absent from available prognostic tools. The greater accessibility of genomic technologies, such as next-generation sequencing (NGS), has enabled clinicians to identify specific genetic alterations that serve as prognostic signals and disease monitoring parameters, cultivating accurate risk profiling that is illustrative of MCL heterogeneity. Through an increased understanding of distinct MCL behaviors, novel therapies that mechanistically target disease biology, including Bruton's tyrosine kinase inhibitors, BCL-2 inhibitors, ROR1 inhibitors, and bispecific T-cell engagers, have broadened the treatment armamentarium for relapsed/refractory MCL cases. These interventions, in addition to chemoimmunotherapy and autologous stem cell transplantation mainstays, confer the individualization of treatment and improved survival outcomes. Further exploration of the considerable biological heterogeneity of MCL can enhance knowledge, management, and the treatment of this rare lymphoma subtype.