Adcetris First FDA-Approved Drug for CD30-Expressing Peripheral T-Cell Lymphomas
On November 16, 2018, the FDA approved brentuximab vedotin (Adcetris; Seattle Genetics), in combination with chemotherapy, for patients with untreated systemic anaplastic large-cell lymphoma (sALCL) or with other CD30-expressing peripheral T-cell lymphomas (PTCLs), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified. This is the first FDA-approved drug for newly diagnosed PTCL, including sALCL. Brentuximab vedotin was previously approved by the FDA for classical Hodgkin lymphoma.
This new indication was based on a double-blind, multicenter clinical trial that randomized 226 patients to brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (CHP) and 226 patients to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). The efficacy was demonstrated by improvement in progression-free survival (PFS). The median PFS was 48.2 months (95% confidence interval [CI], 35.2-not estimable) in the brentuximab vedotin plus CHP arm versus 20.8 months (95% CI, 12.7-47.6) in the brentuximab vedotin plus CHOP arm (hazard ratio [HR], 0.71; 95% CI, 0.54-0.93; P = .011). Improvements with brentuximab vedotin plus chemotherapy were also seen in overall survival (HR 0.66; 95% CI, 0.46-0.95; P = .024), complete response rates in the CHP and CHOP arms (68% vs 56%, respectively; P = .007), and overall response rates (83% vs 72%, respectively; P = .003).
The most common (≥20%) side effects that were more common in the brentuximab vedotin plus CHP arm were nausea, diarrhea, fatigue or asthenia, mucositis, pyrexia, vomiting, and anemia. Peripheral neuropathy was reported in 52% of patients in the CHP arm and 55% in the CHOP arm. The FDA used its new Real-Time Oncology Review Pilot Program to approve this indication, which took <2 weeks to complete.