monomethyl auristatin E (MMAE)- new drug for Hodgkins lymphoma

An investigational drug composed of a monoclonal antibody linked to a potent chemotherapy agent led to complete or substantial tumor shrinkage in nearly 40 percent of patients with Hodgkin lymphoma in a phase I clinical trial, researchers reported November 4, 2010, in the New England Journal of Medicine.

In the trial, 42 patients with Hodgkin lymphoma and three patients with anaplastic large-cell lymphoma (ALCL) who had relapsed after earlier treatments (including stem cell transplantation) or were resistant to standard treatments received the drug brentuximab vedotin (SGN-35). The antibody component of the drug targets a protein called CD30 that sits on the surface of lymphoma cells. Attached to the antibody is a powerful investigational chemotherapy agent called monomethyl auristatin E (MMAE).

Developed by Seattle Genetics, MMAE is 100 to 1,000 times more potent than other chemotherapy drugs, according to the company. The antibody directs the drug to cancer cells, where it is absorbed and degraded by enzymes in the cells’ nuclei, releasing the MMAE and leading to cell death.

Among the 17 patients who had measurable responses, 11 had no evidence of existing cancer (complete response) after treatment, and the remainder had at least 50 percent tumor shrinkage (partial response). Because it was a phase I trial, patients received different doses. Among the 12 patients who received the most effective dose for which side effects were the least severe (the maximum tolerated dose), six had a measurable response. Overall, 86 percent of patients in the trial had at least some tumor shrinkage and side effects were limited.

Over the last 3 decades, there has been little progress in developing new treatments for Hodgkin lymphoma. So, these results offer significant promise for patients, said the study’s lead investigator, Anas Younes, M.D., of the University of Texas M. D. Anderson Cancer Center. “I think it is remarkable that the majority of patients had tumor reductions when they were treated on the phase I study,” he wrote in an e-mail.

Initial results from a phase II trial of the drug in the same patient population appear to be even stronger than the phase I results, according to Seattle Genetics. In late September 2010, the company announced that 75 percent of the 102 patients in the phase II trial, all of whom had relapsed/refractory Hodgkin lymphoma, had an objective response. And, in early October, the company reported that patients with ALCL in another phase II trial of brentuximab had an 86 percent measurable response rate. More complete results and details from both trials will be presented at the American Society of Hematology annual meeting in December 2010.

source- www.cancer.gov