Relapsed or refractory large B-cell lymphoma after chimeric antigen receptor T-cell therapy: Current challenges and therapeutic options

Br J Haematol. 2023 Apr;201(1):15-24. doi: 10.1111/bjh.18656. Epub 2023 Jan 29.

Abstract

Chimeric antigen receptor (CAR) T-cell (CAR-T) therapy can provide durable remission in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after failure of chemoimmunotherapy. However, patients who are refractory or relapsing after CAR-T therapy have poor outcomes. Multiple mechanisms of CAR-T therapy failure have been proposed but management of these patients remains a challenge. As CAR-T therapy moves earlier in the treatment of DLBCL, we urgently need trials focused on patients with relapse after CAR-T therapy. Recent advances in novel immunotherapies such as bispecific antibodies, antibody-drug conjugates and next-generation CAR-T therapies may provide avenues for treatment. Here we review the available data on using these drugs after failure of CAR-T therapy and provide a framework for the ideal sequencing of these novel agents.

Keywords: bispecific monoclonal antibodies; chimeric antigen receptor T-cell therapy; diffuse large B cell; immunotherapy; lymphoma; relapse.

Publication types

  • Review

MeSH terms

  • Antigens, CD19
  • Cell- and Tissue-Based Therapy
  • Humans
  • Immunotherapy, Adoptive / adverse effects
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Neoplasm Recurrence, Local / etiology
  • Receptors, Antigen, T-Cell / therapeutic use
  • Receptors, Chimeric Antigen* / therapeutic use

Substances

  • Receptors, Chimeric Antigen
  • Receptors, Antigen, T-Cell
  • Antigens, CD19