FDA Grants Priority Review to Adcetris Consolidation in Hodgkin Lymphoma

The Food and Drug Administration (FDA) has granted a priority review to the antibody-drug conjugate Adcetris (brentuximab vedotin) as a consolidation therapy following autologous stem cell transplantation (ASCT) in patients with Hodgkin's lymphoma at risk of relapse or progression, based on findings from the phase 3 AETHERA trial. The FDA is scheduled to review the drug by August 18, 2015.

In the AETHERA study, treatment with Adcetris improved progression-free survival (PFS) by 43 percent compared with placebo in patients at high-risk of relapse or with primary refractory Hodgkin's lymphoma immediately following ASCT. Results from the study were presented at the 2014 American Society of Hematology Annual Meeting and subsequently published in The Lancet.

Adcetris was granted an accelerated approval in August 2011 as a treatment for patients with Hodgkin lymphoma after failure of ASCT or after failure of at least two prior chemotherapy regimens in patients who were not candidates for ASCT. The new indication for Adcetris, based on the AETHERA trial, would move treatment with the drug forward, as a therapy for patients who are at high risk of relapse following ASCT.

In AETHERA, 329 patients were randomized to receive Adcetris or placebo. The primary endpoint of the study was PFS.

The median PFS with Adcetris was 42.9 versus 24.1 months. The most common all-grade adverse events with Adcetrisversus placebo were peripheral sensory neuropathy and neutropenia. A majority (85 percent) of patients who experienced peripheral neuropathy with Adcetris had resolution of this adverse event within a median of 23.4 months.

“This is the first study in lymphoma to demonstrate that the addition of a maintenance drug after transplant can markedly improve patient outcomes,” lead investigator Craig Moskowitz, of Memorial Sloan Kettering Cancer Center, said when the results were presented at ASH. “Given these extremely positive results, we predict that brentuximab vedotin will soon become the standard of care for Hodgkin lymphoma patients who undergo an autologous stem cell transplant.”

Adcetris consists of the anti-CD30 monoclonal antibody SGN-30 conjugated to the cytotoxic agent monomethyl auristatin E (MMAE). It continues to be explored in a number of phase 3 clinical trials for patients with hematologic malignancies. The drug is being compared with physician's choice as a treatment for patients with CD30-positive cutaneous T-cell lymphoma. Additionally, Adcetris is being explored in combination with chemotherapy for younger patients with newly diagnosed Hodgkin's lymphoma.