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Posttransplant Brentuximab: New Standard of Care for Hodgkin Lymphoma?

TOP - February 2015, Vol 8, No 1

San Francisco, CA—Early posttransplant consolidation with brentuximab vedotin (Adcetris) significantly improved progression-free survival (PFS) compared with placebo in patients with Hodgkin lymphoma who are at risk for disease progression in the placebo-controlled phase 3 AETHERA trial. AETHERA is the first placebo-­controlled trial to compare brentuximab and placebo in patients with Hodgkin lymphoma after transplant. The results of the study were presented at the 2014 American Society of Hematology annual meeting.

The median PFS was 43 months for the group receiving brentuximab versus 24 months for the group receiving placebo (P = .001), representing a 43% reduction in the risk for disease progression. The 2-year PFS rates were 65% and 45%, respectively, for the cohorts.

“In my opinion, once this study is published, brentuximab should be the standard of care for patients with risk factors for disease progression,” namely, with remission duration <1 year, extranodal disease, B symptoms, 2 or more previous salvage therapies, and primary refractory disease,” stated lead investigator Craig H. Moskowitz, MD, Clinical Director, Division of Hematologic Oncology, Memorial Sloan Kettering Cancer Center, New York. Dr Moskowitz called the 20% difference in 2-year PFS “unprecedented” in any lymphoma.

Autologous stem-cell transplant (ASCT) cures approximately 50% of patients with relapsed or refractory Hodgkin lymphoma. The other 50% will relapse after transplant. Before this study, no investigational regimen had improved posttransplant outcomes.

Brentuximab is an antibody-drug conjugate directed to CD30, which is typically expressed in classic Hodg­kin lymphoma cells. Although brentuximab has been approved by the FDA for the treatment of relapsed or refractory Hodgkin lymphoma and for systemic anaplastic large-cell lymphoma, it is not approved for posttransplant consolidation.

Study Details
The international multicenter trial enrolled 329 patients with Hodgkin lymphoma who had at least 1 risk factor for relapse. Approximately 50% of the patients had ≥3 risk factors for disease progression at baseline. After ASCT, patients were randomized to 16 cycles of treatment with brentuximab or placebo. Of patients in the placebo group who progressed, 85% were crossed over to brentuximab.

Brentuximab achieved superior PFS in all prespecified subgroups, including primary refractory patients who relapsed within 12 months of frontline therapy and patients who relapsed after 12 months with extranodal disease.

The overall survival (OS) was no different between the 2 treatment arms in the interim analysis at 2 years, which could be attributed to the high percentage of patients receiving placebo who crossed over to the active treatment arm. The final OS analysis will be presented in 2016.

The most common adverse events in the brentuximab arm included peripheral sensory neuropathy (56%), neutropenia (35%), upper respiratory tract infection (26%), fatigue (24%), and peripheral motor neuropathy (23%). Dose reductions of brentuximab effectively alleviated peripheral neuropathy in the majority of patients.

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