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The US Food and Drug Administration (FDA) has approved brentuximab vedotin (Adcetris) for use as consolidation treatment after autologous hematopoietic stem cell transplant (auto-HSCT) in patients with classical Hodgkin lymphoma (HL) at high risk of relapse or progression.
The drug is the first FDA-approved consolidation option available to these patients.
The approval was based on results of the phase 3 AETHERA trial.
Results from this trial also served to convert a prior accelerated approval of brentuximab vedotin to regular approval. The drug is now fully approved for the treatment of classical HL patients who have failed auto-HSCT and those who have failed at least 2 prior multi-agent chemotherapy regimens and are not candidates for auto-HSCT.
Brentuximab vedotin is also FDA-approved to treat patients with systemic anaplastic large-cell lymphoma who have failed at least 1 prior multi-agent chemotherapy regimen. The drug has accelerated approval for this indication based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
AETHERA trial
The trial was designed to compare brentuximab vedotin to placebo, both administered for up to 16 cycles (approximately 1 year) every 3 weeks following auto-HSCT. Results from the trial were published in The Lancet in March and presented at the 2014 ASH Annual Meeting.
The study enrolled 329 HL patients at risk of relapse or progression, including 165 on the brentuximab vedotin arm and 164 on the placebo arm.
Patients were eligible for enrollment in the AETHERA trial if they had a history of primary refractory HL, relapsed within a year of receiving frontline chemotherapy, and/or had disease outside of the lymph nodes at the time of pre-auto-HSCT relapse.
Brentuximab vedotin conferred a significant increase in progression-free survival over placebo, with a hazard ratio of 0.57 (P=0.001). The median progression-free survival was 43 months for patients who received brentuximab vedotin and 24 months for patients who received placebo.
The most common adverse events (≥20%), of any grade and regardless of causality, in the brentuximab vedotin arm were neutropenia (78%), peripheral sensory neuropathy (56%), thrombocytopenia (41%), anemia (27%), upper respiratory tract infection (26%), fatigue (24%), peripheral motor neuropathy (23%), nausea (22%), cough (21%), and diarrhea (20%).
The most common adverse events (≥20%), of any grade and regardless of causality, in the placebo arm were neutropenia (34%), upper respiratory tract infection (23%), and thrombocytopenia (20%).
In all, 67% of patients on the brentuximab vedotin arm experienced peripheral neuropathy. Of those patients, 85% had resolution (59%) or partial improvement (26%) in symptoms at the time of their last evaluation, with a median time to improvement of 23 weeks (range, 0.1-138).
