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Exploiting gene mutations and biomarkers to guide treatment recommendations in mantle cell lymphoma

ABSTRACT Introduction: While there has been an improvement in the treatment of mantle cell lymphoma (MCL) in both median progression-free survival (PFS; >7–8 years) and overall survival (OS; >10–12 years), patients with high-risk features such as high risk MIPI (mantle cell international prognostic index), high Ki-67 (≥30%), or blastoid variants still carry poor outcome with a median OS of 3 years. Furthermore, patients with high-risk molecular features, such as TP53 mutations, show dismal outcome, with a median OS of 1.8 years, regardless of therapy used. Further studies have led to the development of six novel drugs approved for the treatment of relapse/refractory (R/R) MCL, leading to improved survival even in refractory or high-risk patients. Areas covered: This review covers clinical biological and molecular features that impact MCL outcome with current standards. Beyond the recognition of separate subentities, we review how high-risk molecular features have paved the way toward a new paradigm away from chemoimmunotherapy. Expert opinion: Progress in novel therapies and in routine diagnostics, particularly next-generation sequencing (NGS), support the development of new treatment strategies, not based on the dose intensity/age dichotomy, which may prevent the need for chemotherapy and improve outcome across MCL including in high-risk subsets.