Mantle Cell Lymphoma in 2026 : A New Era of Precision and Hope

Abstract: Mantle cell lymphoma (MCL) is a heterogeneous B-cell neoplasm with variable clinical behavior, ranging from indolent non-nodal forms to aggressive blastoid or pleomorphic variants. Treatment selection is guided by patient fitness, disease subtype, and molecular risk factors such as TP53 status and Ki-67 proliferation index.For first-line therapy, fit patients typically receive intensive immunochemotherapy with cytarabine-based regimens followed by autologous stem cell transplantation (ASCT) and rituximab maintenance, whereas elderly or unfit patients are managed with bendamustine-rituximab or less intensive chemoimmunotherapy. High-risk patients, including those with TP53 mutations or blastoid morphology, may benefit from early incorporation of targeted therapies such as Bruton tyrosine kinase inhibitors (BTKi) or enrollment in clinical trials.Second-line therapy for relapsed or refractory disease is dominated by BTKi (ibrutinib, acalabrutinib, zanubrutinib) with or without anti-CD20 antibodies, while novel combinations including venetoclax or lenalidomide-rituximab provide additional options. Third-line strategies for multi-refractory MCL increasingly incorporate cellular therapies, including CAR-T cells, as well as investigational targeted agents.Overall, the MCL treatment landscape has evolved from conventional chemotherapy towards precision-targeted and cellular therapies, enabling individualized treatment approaches based on disease biology and patient characteristics.Keywords: Mantle cell lymphoma; first-line therapy; relapsed/refractory; Bruton tyrosine kinase inhibitors; CAR-T cells; TP53 mutation; blastoid variant; blastoid variant