Brentuximab vedotin, sold under the brand name Adcetris, is an antibody-drug conjugate medication used to treat relapsed or refractory Hodgkin lymphoma (HL) and systemic anaplastic large cell lymphoma (ALCL), a type of T cell non-Hodgkin lymphoma. It selectively targets tumor cells expressing the CD30 antigen, a defining marker of Hodgkin lymphoma and ALCL.[1] The drug is being jointly marketed by Millennium Pharmaceuticals outside the US and by Seagen in the US.[2]
Medical uses
In the United States, brentuximab vedotin is indicated for the treatment of Hodgkin lymphoma, systemic anaplastic large cell lymphoma, primary cutaneous anaplastic large cell lymphoma, and CD30-expressing mycosis fungoides.
In the European Union, brentuximab vedotin is indicated for the treatment of Hodgkin lymphoma, systemic anaplastic large cell lymphoma, and cutaneous T cell lymphoma.
Design
Brentuximab vedotin[3] consists of the chimeric monoclonal antibody brentuximab (cAC10, which targets the cell-membrane protein CD30) linked with maleimide attachment groups, cathepsin-cleavable linkers (valine-citrulline), and para-aminobenzylcarbamate spacers to three to five units of the antimitotic agent monomethyl auristatin E (MMAE, reflected by the 'vedotin' in the drug's name).[4] The peptide-based linker bonds the antibody to the cytotoxic compound in a stable manner so the drug is not easily released from the antibody under physiologic conditions to help prevent toxicity to healthy cells and ensure dosage efficiency. The peptide antibody-drug bond facilitates rapid and efficient drug cleavage inside target tumor cell. The antibody cAC10 part of the drug binds to CD30 which often occurs on diseased cells but rarely on normal tissues. The antibody portion of the drug attaches to CD30 on the surface of malignant cells, delivering MMAE which is responsible for the anti-tumour activity.[5][6]
Serious adverse events
Brentuximab vedotin was studied as monotherapy in 160 patients in two phase II trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were chemotherapy-induced peripheral neuropathy (a progressive, enduring and often irreversible tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs), neutropenia (an immune system impairment), fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, fever, rash, thrombocytopenia, cough and vomiting.[9]
Society and culture
Legal status
In August 2011, the US Food and Drug Administration (FDA) granted accelerated approval to the biologics license application (BLA) submitted by Seattle Genetics for the use of brentuximab vedotin[11] in the treatment of relapsed HL and ALCL.[12]
In October 2012, the European Medicines Agency (EMA) gave it conditional marketing authorization for relapsed or refractory HL and ALCL.[13][14]
In November 2017, the FDA approved brentuximab vedotin as a treatment for patients with cutaneous T-cell lymphoma
Research
Clinical trials
In a 2010, clinical trial,[22] 34% of patients with refractory Hodgkin lymphoma achieved complete remission and another 40% had partial remission.[23] Tumor reductions were achieved in 94% of patients. In ALCL, 87% of patients had tumors shrink at least 50% and 97% of patients had some tumor shrinkage.[24]
Reports in 2013, showed interim results[25] from a Phase II, open-label, single-arm study designed to evaluate the antitumor activity of brentuximab vedotin in relapsed or refractory CD30-positive NHL, including B-cell neoplasms. These results demonstrated that single-agent brentuximab vedotin induced a 42% objective response rate and manageable safety profile among advanced diffuse large B-cell lymphoma patients.[26]
References
- Seattle Genetics Submits BLA to FDA for brentuximab vedotin in relapsed or refractory hodgkin lymphoma and systemic ALCL Fierce Biotech, 28 February 2011^
- Takeda and Millennium Announce Approval of Adcetris (Brentuximab Vedotin) in Switzerland www.takedaoncology.com, retrieved 4 June 2020^
- ADC Review / Journal of Antibody-drug Conjugates: Brentuximab Vedotin