Patients with relapsed and difficult-to-treat Hodgkin lymphoma who received brentuximab vedotin following treatment with high-dose chemotherapy and stem cell transplant had an unprecedented 50% higher likelihood of continuing to experience PFS at 2 years.
Craig H. Moskowitz, MD
Patients with relapsed and difficult-to-treat Hodgkin lymphoma who received brentuximab vedotin (Adcetris) following treatment with high-dose chemotherapy and stem cell transplant had an unprecedented 50% higher likelihood of continuing to experience progression-free survival (PFS) at 2 years. This is particularly meaningful because most patients in this population who haven’t experienced relapse 2 years after transplant are cured.
The study’s lead author, Craig Moskowitz, MD, of Memorial Sloan Kettering Cancer Center, reported those results from the phase III, placebo-controlled AETHERA trial at the 2014 ASH Annual Meeting.
While roughly half of patients with this condition are cured through the administration of high-dose chemotherapy and stem cell transplant, consolidation strategies to prolong good health afterward are needed because many others relapse, Moskowitz said.
Brentuximab vedotin is an antibody that targets the CD30 protein on Hodgkin lymphoma cells. The drug has demonstrated an objective response rate of 75% in Hodgkin lymphoma that has relapsed or become refractory after autologous stem cell transplant; the AETHERA trial was initiated to evaluate whether early treatment with brentuximab vedotin after transplant could prevent progression in patients with Hodgkin lymphoma, the authors wrote in the abstract presented at ASH.
The drug was approved by the FDA in August 2011 for the treatment of patients with Hodgkin lymphoma after failure of stem cell transplant, or failure of at least two prior multiagent chemotherapy regimens in patients who are not candidates for transplant. Simultaneously, it was approved for use in patients who have systemic anaplastic large cell lymphoma after the failure of at least one prior multiagent chemotherapy regimen.
“This is the first study in lymphoma to demonstrate that the addition of a maintenance drug after transplant can markedly improve patient outcomes,” Moskowitz said. “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.”
The randomized, multicenter study compared brentuximab vedotin with placebo in 327 patients who had been treated with a minimum of two prior systemic therapies and faced a risk of post-transplant disease progression. All had either achieved remission or had stable, non-progressing disease at the time of stem cell transplant, according to the abstract. Thirty to 45 days after transplant, patients were randomized to receive best supportive care plus either 1.8 mg/kg of brentuximab vedotin or placebo every 3 weeks for up to 16 cycles (approximately 1 year). Patients on the placebo arm who experienced disease progression were allowed to leave the trial and receive brentuximab vedotin as part of a different study.
The primary endpoint was PFS, and secondary endpoints were overall survival and safety and tolerability of the drug.
After a median follow-up of 2 years, researchers found that 65% of patients receiving the drug were still experiencing PFS, compared with 45% of patients receiving placebo (HR = 0.50; 95% CI, 0.36-0.70). In an analysis of blinded, pooled efficacy data, an independent review board found that 63% of patients with Hodgkin lymphoma and risk factors for relapse or progression had continued PFS at 2 years when taking brentuximab vedotin, compared with 51% for those on placebo, meaning that, for the overall study population, the 2-year PFS rate was 54%.
Overall survival, at a rate of 88% at 2 years, was the same in both arms, although that number was confounded by the fact that 85% of patients left the placebo arm to receive brentuximab vedotin, and some patients, upon disease progression, underwent second transplants and were salvaged, Moskowitz said.
The median number of treatment cycles was 15, or about 11 months, and 159 patients received 16 cycles. Reasons patients discontinued treatment included disease progression (n = 93), adverse event (n= 61), patient decision (n = 15), and investigator decision (n = 1).
The most common side effects associated with brentuximab vedotin were peripheral sensory neuropathy, upper respiratory tract infection, neutropenia, fatigue, cough, and pyrexia. These were mostly manageable through dose reductions or delays. There were 50 deaths over the 2-year study period, eight occurring prior to disease progression; two deaths occurred within 40 days of dosing with brentuximab vedotin, the authors reported.
Moskowitz CH, Nadamanee A, Masszi T, et al. The Aethera trial: results of a randomized, double-blind, placebo-controlled phase 3 study of brentuximab vedotin in the treatment of patients at risk of progression following autologous stem cell transplant for Hodgkin lymphoma. Presented at: 2014 ASH Annual Meeting; December 6-9, 2014; San Francisco, CA. Abstract 673.