Following treatment with high-dose chemotherapy and stem cell transplant, patients with relapsed and difficult-to-treat Hodgkin lymphoma who received Adcetris had a higher likelihood of progression-free survival at two years.
Following treatment with high-dose chemotherapy and stem cell transplant, patients with relapsed and difficult-to-treat Hodgkin lymphoma who received Adcetris (brentuximab vedotin) had an unprecedented 50 percent higher likelihood of continuing to experience progression-free survival (PFS) at two years.
This is particularly meaningful because most patients in this population whose cancers haven’t relapsed two years after transplant are cured. The study’s lead author, Craig Moskowitz, of Memorial Sloan Kettering Cancer Center, reported those results from the phase 3 AETHERA trial at the 2014 annual meeting of the American Society of Hematology (ASH).
While roughly half of patients with this condition are cured through the administration of high-dose chemotherapy and stem cell transplant, maintenance strategies to prolong good health afterward are needed because many others relapse, Moskowitz said.
Adcetris is an antibody that targets the CD30 protein on Hodgkin lymphoma cells. The drug has demonstrated an objective response rate of 75 percent 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 Adcetris 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 Food and Drug Administration in August 2011 for the treatment of patients with Hodgkin lymphoma after failure of stem cell transplant, or failure of at least two prior multi-agent 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 multi-agent 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 Adcetris 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 Adcetris or placebo every three weeks for up to 16 cycles.
Patients on the placebo arm who experienced disease progression were allowed to leave the trial and receive Adcetris 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 two years, researchers found that 65 percent of patients receiving the drug were still experiencing PFS, compared with 45 percent of patients receiving placebo. In an analysis of blinded, pooled efficacy data, an independent review board found that 63 percent of patients with Hodgkin lymphoma and risk factors for relapse or progression had continued PFS at two years when taking Adcetris compared with 51 percent for those on placebo, meaning that, for the overall study population, the two-year PFS rate was 54 percent. Overall survival, at a rate of 88 percent at two years, was the same in both arms, although that number was confounded by the fact that 85 percent of patients left the placebo arm to receive Adcetris, and some patients, upon disease progression, underwent second transplants and were salvaged, Moskowitz said.
The most common side effects were peripheral sensory neuropathy, upper respiratory tract infection, neutropenia, fatigue, cough and fever. These were mostly manageable through dose reductions or delays. There were 50 deaths over the two-year study period, eight occurring prior to disease progression; two deaths occurred within 40 days of dosing with Adcetris, the authors reported.