Credit: Linda Bartlett
The Japanese Ministry of Health, Labour and Welfare has approved brentuximab vedotin (Adcetris) for the treatment of patients with relapsed or refractory, CD30+ Hodgkin lymphoma (HL) or anaplastic large-cell lymphoma (ALCL).
The approval was based on a phase 1/2 trial in Japanese patients with relapsed or refractory, CD30+ HL or systemic ALCL, as well as data from two phase 2 trials—one of 102 HL patients and one of 58 patients with ALCL.
Brentuximab vedotin is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.
The conjugate employs a linker system designed to be stable in the bloodstream but release monomethyl auristatin E upon internalization into CD30-expressing tumor cells.
Brentuximab vedotin was approved by the US Food and Drug Administration (FDA) in August 2011 and gained conditional approval from Health Canada in February 2013 for the following indications:
- To treat HL patients who had failed autologous stem cell transplant (auto-SCT) or were not eligible for auto-SCT and had failed at least 2 prior multi-agent chemotherapy regimens
- To treat patients with systemic ALCL after they failed at least 1 multi-agent chemotherapy regimen.
The drug received conditional marketing authorization by the European Commission in October 2012 to treat:
- Adult patients with relapsed or refractory, systemic ALCL
- Adults with relapsed or refractory, CD30-positive HL who had undergone auto-SCT or received 2 prior therapies when auto-SCT or multi-agent chemotherapy were not appropriate.
The FDA has granted brentuximab vedotin orphan designation to treat mycosis fungoides. And trials have suggested the drug is active in diffuse large B-cell lymphoma, as well as leukemias and multiple myeloma.
However, brentuximab vedotin also made the FDA watch list due to adverse events associated with the drug’s use. The FDA added a boxed warning to the drug’s label in January 2012, after 3 cases of progressive multifocal leukoencephalopathy were reported in patients receiving brentuximab vedotin.
