Refining risk-stratification for mantle cell lymphoma: integrating novel combination treatments and personalized approaches

INTRODUCTION: Mantle cell lymphoma is a biologically heterogeneous B-cell lymphoma characterized by highly variable clinical outcomes. This review discusses the evolution of risk stratification and emerging treatment approaches, highlighting the need for personalized and risk-adapted treatment strategies. AREAS COVERED: This review examines the evolution of risk stratification in mantle cell lymphoma, from clinical prognostic models to molecular and dynamic biomarkers, such as TP53 mutation, genomic profiling, minimal residual disease, and circulating tumor DNA. Emerging therapeutic approaches, including targeted combinations, chemotherapy-free regimens, cellular immunotherapy and minimal residual disease-driven strategies, are critically reviewed. The literature search was conducted using PubMed (MEDLINE) and updated through June 2026. EXPERT OPINION: Risk stratification is increasingly shifting from traditional clinical models toward integrated biological and genomic models that better capture disease heterogeneity and support personalized and risk adapted treatment. Emerging evidence supports novel chemo-free targeted combinations, particularly for high-risk patients while further research is needed to refine treatment selectin and identify additional determinants of prognosis and treatment resistance in lower risk disease.