Anticancer agent – brentuximab vedotin

Anaplastic large cell lymphoma and Hodgkin’s lymphoma are curable, but a third of patients relapse after therapy

Anaplastic large cell lymphoma and Hodgkin’s lymphoma are curable, but a third of patients relapse after therapy. A new potential treatment is being developed by Seattle Genetics in collaboration with Millennium.

Brentuximab vedotin is a chimeric anti-CD30 antibody, which has been conjugated to monomethylauristatin E, an antitubulin compound using an enzyme-cleavable linker.1 CD30 is highly expressed on both Hodgkin’s and HLCL cells and is highly restricted to cancer cells, thus making it a good target for immunotherapy with monoclonal antibodies, but previous attempts have showed negligible activity.

In a Phase I, open label dose escalation study, a total of 45 patients with relapsed or refractory CD30-positive blood cancers, largely HL and ALL, were given the conjugate in doses of 0.1 to 3.6mg/kg every three weeks.2 All had received previous chemotherapy regimens, with a median of three and a maximum of seven, and nearly three-quarters had undergone autologous stem cell transplantation.

The maximum tolerated dose was 1.8mg/kg, and 17 patients had an objective response, including 11 complete remissions. Half of the 12 who received 1.8mg/kg had an objective response. The most common adverse events were fatigue, nausea, diarrhoea, pyrexia, neutropoenia and peripheral neuropathy. It is now in Phase III trials for relapsed and refractory forms of these two lymphomas.

references

1. S.O. Doronina et al. Nature Biotech. 2003, 21, 778

2. A. Younes et al. N. Engl. J. Med. 2010, 363, 1812

Companies