Antibody-drug conjugates for previously treated aggressive lymphomas: focus on polatuzumab vedotin

Expert Rev Clin Pharmacol. 2020 Oct;13(10):1073-1083. doi: 10.1080/17512433.2020.1826303. Epub 2020 Oct 5.

Abstract

Introduction: Antibody-drug conjugates (ADCs) are immunoconjugates and comprise a monoclonal antibody that is chemically attached to a cytotoxic drug (or payload) via a stable chemical linker. Since the approval of the first ADC in 2000, there are now nine different approved agents and over 100 ADCs in the drug-development pipeline.

Areas covered: This review briefly describes the ADCs approved for treatment of lymphoma and their distinguishing factors in terms of target, linker and payload. The clinical implications of the use of ADCs are also considered. Here, we focus on polatuzumab vedotin, an ADC targeted to CD79b, which is approved for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) who have received at least one (EU approval) or two (US approval) prior therapies and are not eligible for bone marrow transplantation. The characteristics of polatuzumab vedotin are discussed and clinical data are presented. The future of polatuzumab vedotin clinical development, and ADCs in general, are also considered.

Expert opinion: ADCs represent a significant advance in the treatment of lymphoma. Polatuzumab vedotin has shown clinical efficacy and a tolerable safety profile in both first-line and R/R DLBCL; future studies are planned to further investigate this ADC.

Keywords: Antibody-drug conjugate; DLBCL; NHL; monoclonal antibody; polatuzumab vedotin.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / pharmacology
  • CD79 Antigens / immunology*
  • Humans
  • Immunoconjugates / administration & dosage*
  • Immunoconjugates / adverse effects
  • Immunoconjugates / pharmacology
  • Lymphoma / drug therapy*
  • Lymphoma / pathology
  • Lymphoma, Large B-Cell, Diffuse / drug therapy
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Recurrence

Substances

  • Antibodies, Monoclonal
  • CD79 Antigens
  • CD79B protein, human
  • Immunoconjugates
  • polatuzumab vedotin