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<p>Mantle cell lymphoma (MCL) is a biologically and clinically heterogeneous B-cell malignancy with a historically poor prognosis. Recent advances have substantially expanded treatment options, particularly through the integration of targeted therapies, chemotherapy-free regimens, and cellular approaches. Frontline treatment now incorporates Bruton’s tyrosine kinase inhibitors (BTKi) in combination with chemotherapy and in chemotherapy-free regimens. For patients with relapsed or refractory disease, particularly those previously exposed to BTKi, chimeric antigen receptor T-cell (CAR T) therapies and third-generation BTKi like pirtobrutinib provide highly effective options while several novel agents, including bispecific antibodies (bsAbs), are under investigation. Nevertheless, achieving long-lasting remissions is still a major challenge, especially among high-risk patients. Future directions include optimizing sequencing, refining rational combination therapies, expanding the application of bsAbs, and integrating small molecules and novel immunoconjugates to enhance therapeutic efficacy and long-term outcomes. This review provides an overview of the current and emerging therapies for MCL, highlighting how the integration of biological agents, strategic combinations, and patient-centered approaches are driving the next phase of MCL treatment.</p>

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Evolving therapeutic strategies in mantle cell lymphoma: advancements and future directions

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月15日

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  • Rita Tavarozzi,
  • Nawar Maher,
  • Gioacchino Catania,
  • Giulia Zacchi,
  • Francesca D’Andrea,
  • Antonella Sofia,
  • Manuela Zanni,
  • Marco Ladetto

摘要

Mantle cell lymphoma (MCL) is a biologically and clinically heterogeneous B-cell malignancy with a historically poor prognosis. Recent advances have substantially expanded treatment options, particularly through the integration of targeted therapies, chemotherapy-free regimens, and cellular approaches. Frontline treatment now incorporates Bruton’s tyrosine kinase inhibitors (BTKi) in combination with chemotherapy and in chemotherapy-free regimens. For patients with relapsed or refractory disease, particularly those previously exposed to BTKi, chimeric antigen receptor T-cell (CAR T) therapies and third-generation BTKi like pirtobrutinib provide highly effective options while several novel agents, including bispecific antibodies (bsAbs), are under investigation. Nevertheless, achieving long-lasting remissions is still a major challenge, especially among high-risk patients. Future directions include optimizing sequencing, refining rational combination therapies, expanding the application of bsAbs, and integrating small molecules and novel immunoconjugates to enhance therapeutic efficacy and long-term outcomes. This review provides an overview of the current and emerging therapies for MCL, highlighting how the integration of biological agents, strategic combinations, and patient-centered approaches are driving the next phase of MCL treatment.