This VJHemOnc podcast episode explores future directions in frontline mantle cell lymphoma (MCL) treatment, focusing on the evolving role of chemotherapy, BTK inhibitors, and autologous stem cell transplantation. Mats Jerkeman, MD, PhD, Lund University, Lund, Sweden, shares a European perspective on changing frontline treatment standards, including the implications of the TRIANGLE and ECHO trials and the challenges of treating patients with high-risk disease. Jonathon Cohen, MD, MS, Winship Cancer Institute of Emory University, Atlanta, GA, discusses patient selection for chemotherapy-free approaches, the role of TP53 mutations and measurable residual disease (MRD) in treatment decisions, and emerging therapies, including BTK degraders, CAR T-cell therapy, and bispecific antibodies. Together, the experts explore how biological risk factors may increasingly guide treatment selection and consider the approaches that could shape the future of frontline MCL management.