Your chemo is no good here: management of high-risk MCL.

Historically considered a lymphoma with limited treatment options and poor outcomes, the treatment landscape in mantle cell lymphoma (MCL) has evolved remarkably in the last decade. Chemoimmunotherapy (CIT) remains the primary frontline treatment for most patients with MCL, typically with an intensive approach in younger and fit patients. The role of consolidative autologous stem cell transplantation remains controversial, with recent data further questioning its benefit. Novel agents have shown promising results in recent frontline clinical trials and challenge the current paradigm in MCL, particularly in high-risk patients who generally have poor outcomes with CIT. Risk stratification is key to incorporating novel agents in the frontline treatment of MCL, identifying patients who do not benefit from or could be spared CIT, guiding treatment intensity and duration, and improving overall outcomes, including safety and quality of life. The MCL International Prognostic Index and Ki-67 play an important role in identifying patients with high-risk MCL. TP53 aberrations, particularly mutations, currently identify patients with the highest risk, limited benefit from CIT, and greatest need for novel therapies. Other genetic aberrations and biological clusters are being identified but currently have limited clinical utility.