Approaches to the management of relapsed/refractory mantle cell lymphoma: navigating an increasingly complex therapeutic landscape

Expert Rev Hematol. 2026 Mar;19(3):269-280. doi: 10.1080/17474086.2026.2613730. Epub 2026 Jan 12.

Abstract

Introduction: Mantle cell lymphoma (MCL) represents a distinct subtype of mature B-cell lymphoma, considered incurable with a pattern of recurrent relapses and suboptimal responses to subsequent therapies that portend poorer prognosis with each recrudescent disease.

Areas covered: Covalent and non-covalent Bruton tyrosine kinase inhibitors (BTKi) have transformed the therapeutic landscape of relapsed/refractory (R/R) MCL as monotherapies though these drug classes may emerge to be more effective as combinations with B-cell lymphoma-2 (BCL-2) inhibitors and immunotherapy. Immune-leveraging therapies, including chimeric antigen receptor (CAR) T-cell therapy and T-cell engaging antibodies, are gaining momentum, with the former demonstrating durable responses in a subset of patients, while the latter being evaluated in various combination regimens. Allogeneic hematopoietic stem cell transplants remain a potentially curative option for selected patients.

Expert opinion: This review seeks to navigate this increasingly complex therapeutic landscape while providing a suggested treatment and sequencing algorithm that may be tailored to individual patients.

Keywords: CAR T; MCL; Mantle cell lymphoma; bispecific; expert opinion; how to treat; non-covalent BTK inhibitor; refractory; relapsed; review.

Publication types

  • Review

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors
  • Combined Modality Therapy
  • Disease Management
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunotherapy / methods
  • Immunotherapy, Adoptive
  • Lymphoma, Mantle-Cell* / diagnosis
  • Lymphoma, Mantle-Cell* / pathology
  • Lymphoma, Mantle-Cell* / therapy
  • Protein Kinase Inhibitors / therapeutic use
  • Recurrence

Substances

  • Protein Kinase Inhibitors
  • Agammaglobulinaemia Tyrosine Kinase