High time for risk-adapted treatment in mantle cell lymphoma

Mantle cell lymphoma has multiple treatment options, yet the disease is difficult to cure. Relapses are common, treatments can cause severe side-effects, and current recommendations are still largely based on age rather than biology. Although suitability for intensive treatment was previously the decisive parameter, increasing knowledge on the biology of mantle cell lymphoma and less toxic targeted therapies has made non-risk adapted treatments outdated. TP53 mutations or deletions, blastoid histology, and a high Ki-67 proliferation index consistently identify patients at high risk of relapse. Additionally, positive measurable residual disease serves as a powerful surrogate endpoint to identify patients with an inadequate treatment response who might benefit from treatment modification. Similarly, markers of indolent mantle cell lymphoma, toxicity, and tolerability need to be further refined and might permit chemotherapy-free approaches. We outline future initiatives aimed at refining risk stratification, harmonising treatment, and integrating multiparameter biomarkers to improve prognosis and provide the biological rational for combination strategies. These efforts are essential to accelerate the translation of biological insights into clinical practice.