Could bystander killing contribute significantly to the antitumor activity of brentuximab vedotin given with standard first-line chemotherapy for Hodgkin lymphoma?. (April 2014)

• Record Type: Journal Article
• Authors: Brown, Michael P; Staudacher, Alexander H
• Is Part Of: Immunotherapy. Volume 6:Number 4(2014:Apr.)
• Page Start: 371
• Page End: 375
• Publication Date: 2014-04
• Subjects: antibody–drug conjugate -- bystander effect -- cathepsin; Immunotherapy -- Periodicals; 615.37
• DOI: 10.2217/imt.14.13
• Languages: English
• ISSNs: 1750-743X

Abstract

Evaluation of: Younes A, Connors JM, Park SI et al. Brentuximab vedotin combined with ABVD or AVD for patients with newly diagnosed Hodgkin's lymphoma: a Phase 1, open-label, dose-escalation study. Lancet Oncol . 14(13), 1348–1356 (2013). With exceptionally high response rates, the CD30-directed antibody–drug conjugate brentuximab vedotin (BV) was US FDA approved for treatment of patients with relapsed/refractory Hodgkin lymphoma (HL). Now in Phase I clinical trial, it has been shown that combining BV with multiagent chemotherapy (excluding bleomycin) as first-line treatment in HL patients with high-risk disease is feasible. Complete response rates were over 90% and toxicity was manageable. Given that the malignant cell population comprises a minority of HL lesions, and that BV releases a diffusible cytotoxin via a cathepsin B-cleavable linker, we argue that a significant proportion of the antitumor activity of BV can be attributed to bystander cytotoxicity in addition to direct killing of CD30-expressing malignant cells.