Brentuximab vedotin for the treatment of Hodgkin’s lymphoma

Abstract

Although Hodgkin’s lymphoma is considered a highly curable cancer, a substantial portion of patients will be refractory or will relapse after first-line therapies and even after subsequent autologous stem cell transplantation. With the absence of effective salvage therapies, these patients carry a poor prognosis with dismal survival. In this therapeutic void, the antibody–drug conjugate brentuximab vedotin was introduced and has since yielded impressive and durable response with minimal and reversible toxicity. Such efficacy in the relapse-refractory setting has led to new hypotheses and dramatic changes in our treatment strategies of Hodgkin’s lymphoma. Numerous clinical trials evaluating brentuximab in the frontline and various other treatment settings are forthcoming and will demonstrate the full extent of the drug’s impact.

Keywords:

• allogeneic stem cell transplantation
• antibody–drug conjugate
• autologous stem cell transplantation
• brentuximab vedotin
• CD30
• Hodgkin’s lymphoma
• Reed–Sternberg
• refractory disease
• relapsed disease

Financial & competing interests disclosure

R Chen has received honoraria and research funding from Seattle Genetics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Brentuximab vedotin (BV) is an antibody–drug conjugate composed of chimeric IgG1 antibody cAC10, specific for human CD30, the microtubule disrupting agent monomethylauristatin E, and protease-cleavable linker that covalently attaches monomethylauristatin E to cAC10.

• BV is well tolerated with most common adverse effects being peripheral neuropathy, and neutropenia – both reversible with cessation or dose reduction of the drug.

• At the present time, the US FDA indication for BV is in the treatment of patients with Hodgkin’s lymphoma after failure of autologous stem cell transplantation or after failure of at least two prior multi-agent chemotherapy regimens who are transplant candidates and for patients with systemic anaplastic large cell lymphoma after of at least one prior multi-agent chemotherapy regimen.

• BV is currently being explored in various settings of treatment relative to stem cell transplantation as well as upfront therapy for untreated Hodgkin’s lymphoma patients.