Brentuximab Vedotin: A Review in CD30-Positive Hodgkin Lymphoma

Abstract

Intravenous brentuximab vedotin (ADCETRIS^®) is a targeted antibody-drug conjugate (ADC) active against CD30-positive cancer cells such as those associated with classical Hodgkin lymphoma (HL). In noncomparative, phase 2 trials and in the real-world setting, salvage therapy with brentuximab vedotin resulted in high objective response (complete plus partial remission) rates in patients with relapsed or refractory CD30-positive HL, including as retreatment in patients who had an objective response to previous brentuximab vedotin therapy and subsequently relapsed. These beneficial outcomes were durable during long-term follow-up. As consolidation therapy after autologous haematopoietic stem cell transplant (ASCT) in the multinational, phase 3 AETHERA trial, brentuximab vedotin prolonged progression-free-survival (PFS) compared with placebo at a median follow-up of 30 months (primary analysis), with a 43% reduction in the risk of disease progression or death. The beneficial effects of brentuximab vedotin consolidation therapy were maintained during long-term follow-up. In the clinical trial and real-world setting, brentuximab vedotin had an acceptable tolerability and safety profile, with most adverse events manageable with dose reductions and/or delays [including peripheral sensory neuropathy (PSN) and neutropenia]. With a paucity of treatments available for many patients with relapsed or refractory HL, brentuximab vedotin represents an important option for the management of patients who have failed high-dose chemotherapy/ASCT or at least two prior chemotherapy regimens and as post-ASCT consolidation therapy in patients who are at increased risk/high-risk of relapse or progression after ASCT.

Fig. 1

Mechanism of action of brentuximab vedotin in a CD30-positive tumour cell [6, 10, 11]. a Brentuximab vedotin binds to the CD30 membrane receptor. b The CD30-drug complex is internalized and traffics to a lysosome, where enzymes cleave the linker between the antibody and monomethyl auristatin E (MMAE), a microtubule-disrupting agent. c MMAE is released intracellularly, where it d binds to tubulin (leading to G2/M cell cycle arrest and concurrent induction of apoptosis), and extracellularly into the surrounding area, where MMAE may induce apoptosis in surrounding cells (bystander effect), irrespective of CD30 status. Reproduced from Garnock-Jones [13]