Consolidation therapy with brentuximab vedotin can improve progression-free survival (PFS) for Hodgkin lymphoma (HL) patients who have undergone a transplant, according to a phase 3 study.
The trial, known as AETHERA, is a comparison of single-agent brentuximab vedotin to placebo in patients with HL who were at risk of relapse following autologous stem cell transplant (ASCT).
Brentuximab vedotin conferred a 75% improvement in PFS over placebo.
However, there was no significant difference in overall survival between the 2 treatment arms.
These results were recently announced by Seattle Genetics Inc. and Takeda Pharmaceutical Company Limited, the companies developing brentuximab vedotin (Adcetris).
The companies said more complete results from AETHERA will be presented at the 2014 ASH Annual Meeting in December.
AETHERA is a randomized, double-blind, placebo-controlled study designed to evaluate the potential of brentuximab vedotin to extend PFS post-ASCT in patients with HL who have at least one risk factor for progression. In addition to the primary endpoint of PFS, secondary endpoints included overall survival, safety, and tolerability.
Patients were eligible if they had risk factors for residual HL, defined as a history of refractory HL, those who relapse or progress within a year of receiving frontline chemotherapy, and/or those who have disease outside of the lymph nodes at the time of pre-ASCT relapse.
The study included 329 patients who received brentuximab vedotin or placebo every 3 weeks for up to a year.
The researchers assessed PFS a minimum of 2 years after the initiation of treatment for all patients. There was a significant improvement in PFS with brentuximab vedotin compared to placebo (hazard ratio=0.57; P=0.001).
However, a prespecified interim analysis of overall survival showed no significant difference between the treatment arms.
Patients in both arms who experienced progression received a variety of subsequent therapies. Most patients on the placebo arm received brentuximab vedotin after progression.
A further analysis of overall survival is planned in 2016. The safety profile of brentuximab vedotin in the AETHERA trial was generally consistent with the existing prescribing information.
“We anticipate reporting more complete AETHERA data at the ASH Annual Meeting in December and intend to submit a supplemental Biologics License Application to the FDA in 2015 for approval in this setting,” said Clay B. Siegall, PhD, President and Chief Executive Officer of Seattle Genetics.
The FDA has already granted brentuximab vedotin accelerated approval to treat HL patients after ASCT failure or after the failure of at least 2 prior multiagent chemotherapy regimens in patients who are not ASCT candidates. The FDA also granted the drug accelerated approval to treat systemic anaplastic large cell lymphoma after the failure of at least 1 prior multiagent chemotherapy regimen.
The European Commission granted brentuximab vedotin conditional marketing authorization for the same indications. In both cases, the drug can gain full, traditional approval once studies have shown it confers a clinical benefit.
Brentuximab vedotin has a boxed warning detailing the risk of progressive multifocal leukoencephalopathy associated with use of the drug. The drug has also been shown to pose a risk of pulmonary toxicity when combined with bleomycin.
