AETHERA Results Support Brentuximab Vedotin Consolidation Therapy in Hodgkin’s Lymphoma

Early brentuximab vedotin consolidation treatment improves prognosis in high-risk Hodgkin’s lymphoma patients previously treated with autologous stem cell transplantation

medwireNews: Consolidation therapy with brentuximab vedotin soon after autologous stem cell transplantation (ASCT) results in markedly extended progression-free survival (PFS) compared with placebo in patients with relapsed or refractory classic Hodgkin’s lymphoma, research findings suggest.

The anti-CD30 Antibody– monomethyl auristatin E conjugate provides an “important” therapeutic option for this patient population, say Craig Moskowitz, from Memorial Sloan Kettering Cancer Center in New York, USA, and co-investigators.

Of the 329 patients included in the phase III AETHERA trial, 165 were randomly assigned to receive intravenous brentuximab vedotin 1.8 mg/kg on the first day of a 3-week treatment cycle within 35 to 45 days of ASCT for a maximum of 16 cycles. The remaining 164 participants were given placebo delivered similarly.

After a median follow-up of 30 months, median independently assessed PFS was 42.9 months in the brentuximab vedotin arm and 24.1 months in the placebo arm, with a significant hazard ratio of 0.57.

Based on this data, the estimated 2-year PFS rate was 63% and 51% for patients given brentuximab vedotin and placebo, respectively.

Overall survival was comparable between the groups, but crossover was permitted, and 85% of placebo-treated patients went on to receive brentuximab vedotin, the team notes.

Adverse events of grade 3 or higher occurred in 56% of participants in the brentuximab vedotin group and in 32% of those in the placebo group, with neutropenia and peripheral sensory neuropathy the most common toxicities in the brentuximab vedotin-treated patients.

Severe infections of grade 3 or higher were observed in 7% and 6% of patients in the brentuximab vedotin and placebo arms, respectively.

A third of the patients given brentuximab vedotin discontinued treatment as a result of adverse events, the researchers report, but add that the study drug had a “favourable” tolerability profile, indicating that “brentuximab vedotin therapy could be initiated early after [ASCT], when tumour burden is lowest and consolidation might provide the most effect.”

They conclude in The Lancet: “Consolidation therapy with brentuximab vedotin might increase the possibility of cure or potentially avoid exposure to subsequent toxic therapies, and seems to be effective in this young cancer population with high unmet need.”

In an accompanying commentary, Andreas Engert, from University Hospital of Cologne in Germany, agrees that this a “promising” approach, but queries whether the patient population is indeed high risk, given a PFS of “about 50% at 24 months in the placebo group”.

He concludes: “An international consortium is currently reassessing the effect of risk factors in patients with relapsed Hodgkin’s lymphoma to define a high-risk patient population in need of consolidation treatment.

“We look forward to a better definition of patients with relapsed Hodgkin’s lymphoma who should receive consolidation treatment with brentuximab vedotin.”

References

Moskowitz CH, Nademanee A, Masszi T, et al. Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin’s lymphoma at risk of relapse or progression (AETHERA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 2015; Advance online publication 18 March. doi:10.1016/S0140-6736(15)60165-9

Engert A. Hodgkin's lymphoma: who needs consolidation treatment? Lancet 2015; Advance online publication 18 March. doi:10.1016/S0140-6736(15)60583-9

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