ABCs of ADCs in management of relapsed/refractory diffuse large B-cell lymphoma

Blood Rev. 2022 Nov:56:100967. doi: 10.1016/j.blre.2022.100967. Epub 2022 Apr 22.

Abstract

In the past 5 years, 3 chimeric antigen receptor (CAR) T-cell therapies, 2 antibody-drug conjugates (ADCs), 1 CD19-directed monoclonal antibody, and 1 exportin-1 inhibitor have been approved by the Food and Drug Administration for patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). The noncellular therapies received accelerated approval based on the overall response rate in clinical trials that differ in multiple aspects of the patient populations enrolled, including age, performance status, prior lines of therapy, and inclusion of patients with primary refractory DLBCL, transformed lymphoma, or high-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6. ADCs approved for DLBCL differ in target antigen, antibody structure, linker, and cytotoxin, which results in a different safety and efficacy profile. Here, we comprehensively review the current knowledge of recently approved and emerging strategies for the management of R/R DLBCL with a focus on ADCs.

Keywords: (6 maximum): Lymphoma; Antibody-drug conjugate; Diffuse large B-cell lymphoma; Loncastuximab tesirine; Relapsed/refractory.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / therapeutic use
  • Cytotoxins / therapeutic use
  • Humans
  • Immunoconjugates* / therapeutic use
  • Karyopherins
  • Lymphoma, Large B-Cell, Diffuse* / drug therapy
  • Lymphoma, Large B-Cell, Diffuse* / pathology
  • Lymphoma, Non-Hodgkin*
  • Neoplasm Recurrence, Local / drug therapy
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Chimeric Antigen* / therapeutic use

Substances

  • Immunoconjugates
  • Receptors, Chimeric Antigen
  • Antibodies, Monoclonal
  • Proto-Oncogene Proteins c-bcl-2
  • Karyopherins
  • Cytotoxins