Anti-CD30 antibody-drug conjugate therapy in lymphoma: current knowledge, remaining controversies, and future perspectives

Ann Hematol. 2023 Jan;102(1):13-29. doi: 10.1007/s00277-022-05054-9. Epub 2022 Dec 13.

Abstract

CD30 is overexpressed in several lymphoma types, including classic Hodgkin lymphoma (cHL), some peripheral T-cell lymphomas (PTCL), and some cutaneous T-cell lymphomas. The antibody-drug conjugate brentuximab vedotin targets CD30-positive cells and has been evaluated for the treatment of various lymphoma entities. This narrative review summarizes 10 years of experience with brentuximab vedotin for the treatment of CD30-positive lymphomas, discusses novel therapies targeting CD30 in development, and highlights remaining controversies relating to CD30-targeted therapy across lymphoma types. The collective body of evidence for brentuximab vedotin demonstrates that exploitation of CD30 can provide sustained benefits across a range of different CD30-positive lymphomas, in both clinical trials and real-world settings. Preliminary experience with brentuximab vedotin in combination with immune checkpoint inhibitors for relapsed/refractory cHL is encouraging, but further exploration is required. The optimal use of brentuximab vedotin for first-line therapy of PTCL remains to be determined. Further research is required on brentuximab vedotin treatment in high-risk patient populations, and in rare lymphoma subtypes, for which no standard of care exists. Novel therapies targeting CD30 include chimeric antigen receptor therapies and bispecific antibody T-cell engagers, which may be expected to further improve outcomes for patients with CD30-positive lymphomas in the coming years.

Keywords: Antibody–drug conjugate; Brentuximab vedotin; CD30 expression; Classic Hodgkin lymphoma; Cutaneous T-cell lymphoma; Peripheral T-cell lymphoma.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • Brentuximab Vedotin / therapeutic use
  • Hodgkin Disease* / pathology
  • Humans
  • Immunoconjugates*
  • Ki-1 Antigen
  • Lymphoma, T-Cell, Cutaneous*
  • Lymphoma, T-Cell, Peripheral* / drug therapy
  • Skin Neoplasms* / drug therapy

Substances

  • Brentuximab Vedotin
  • Ki-1 Antigen
  • Immunoconjugates
  • Antineoplastic Agents