Advances in biomarkers for mantle cell lymphoma in the era of targeted therapies

Exciting therapeutic advances are transforming the mantle cell lymphoma (MCL) treatment landscape, with an expanding array of novel agents. Growing evidence demonstrates that MCL is a biologically heterogeneous disease ineffectively managed with historical uniform standard chemoimmunotherapy approaches. Furthermore, traditional prognosticators such as the MCLInternational prognostic index (MIPI), proliferation index Ki-67, and presence of TP53 aberrations remain valuable but are insufficient to fully capture disease complexity or guide personalised therapy. Biomarker technologies are evolving rapidly. Reflecting this technological renaissance, recent studies have identified a range of novel molecular and cytogenetic alterations that carry prognostic or therapeutic relevance in the context of both chemotherapy and novel agent delivery. Advances in measurable residual disease detection using PCR, next-generation sequencing, and circulating tumour DNA are reshaping risk stratification and offer the potential to guide therapy intensity and duration. New information is emerging regarding the critical role of the tumour microenvironment and immune dysregulation in driving treatment resistance. Additionally, the expanding utility of FDGPET by harnessing quantitative parameters and radiomic data offers new opportunities for multimodality risk stratification. Here, we comprehensively review the literature beyond established MCL prognosticators and provide an overview of these newer prognostic and predictive biomarkers for MCL in modern treatment paradigms, and their role in informing treatment decisions and future research directions.