title: Could bystander killing contribute significantly to the antitumor activity of brentuximab vedotin given with standard first-line chemotherapy for Hodgkin lymphoma?
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.
authors.affiliation: Cancer Clinical Trials Unit, MDP 11, Level 4, East Wing, Royal Adelaide Hospital Cancer Centre, Adelaide, SA, 5000, Australia.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Brown
authors.forename: Alexander H
authors.initials: AH
authors.lastname: Staudacher
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D005260:Female; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage*; D008297:Male
chemical_list: D018796:Immunoconjugates