Brentuximab Vedotin Receives Expanded Approval for Hodgkin Lymphoma Patients

Seattle Genetics, Inc. recently announced patients with classical Hodgkin lymphoma (HL) at high risk of relapse or progression now have a new treatment option.¹ The US Food and Drug Administration (FDA) has expanded its approval of ADCETRIS® (brentuximab vedotin) as a post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation treatment for patients with classical HL at high risk of relapse or progression. This makes brentuximab vedotin the first FDA-approved agent for post-auto-HSCT consolidation treatment for this patient population.

Brentuximab vedotin previously received FDA approval for two indications: classical Hodgkin lymphoma after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, and systemic anaplastic large cell lymphoma (sALCL) in patients who have become refractory in at least one prior multi-agent chemotherapy regimen.

This treatment may now provide an important therapeutic option for patients undergoing autologous stem cell transplantation. Currently, high-dose therapy followed by auto-HSCT is the standard of care for patients with relapsed or primary refractory HL, and approximately 50% of patients may be cured after autologous stem-cell transplantation. However, many patients with unfavorable risk factors progress after transplantation. Brentuximab vedotin is a type of monoclonal antibody directed to the protein CD30, which is expressed in classical HL and systemic anaplastic large cell lymphoma (sALCL).

The FDA decision was based on the positive results from a phase 3 clinical trial called AETHERA. The trial data were published online in The Lancet in March 2015.² The AETHERA trial was a randomized, double-blinded, placebo-controlled study that evaluated the potential of single-agent brentuximab vedotin to extend progression-free survival (PFS) post-auto-HSCT in patients with HL who had at least one risk factor for progression or relapse.  A risk factor for progression or relapse was defined by at least one of the following: relapse < 12 months after frontline therapy or relapse > 12 months with extranodal disease.

In this study, a total of 329 HL patients at risk of relapse or progression were enrolled, including 165 in the brentuximab vedotin arm and 164 in the placebo arm. The trial achieved its primary endpoint and demonstrated a significant increase in PFS with a hazard ratio of 0.57. The median PFS was 43 months for patients who received brentuximab vedotin compared to 24 months for patients who received placebo.

Brentuximab vedotin-treated patients received a median of 15 treatment cycles (range: 1 to 16) and it was deemed that this treatment had generally acceptable tolerability and a manageable adverse reaction profile. Patients in the placebo arm also received a median of 15 treatment cycles (range: 1 to 16).  

Adverse reactions that led to dose delays in more than 5% of brentuximab vedotin-treated patients were neutropenia (22%), peripheral sensory neuropathy (16%), upper respiratory tract infection (6%), and peripheral motor neuropathy (6%). Adverse reactions led to treatment discontinuation in 32% of brentuximab vedotin-treated patients. Those adverse reactions included peripheral sensory neuropathy (14%), peripheral motor neuropathy (7%), acute respiratory distress syndrome (1%), paraesthesia (1%), and vomiting (1%).

References:

• Seattle Genetics, Inc. (2015). Adcentris now approved for the treatment of patients with classical Hodgkin lymphoma (HL) at high risk of relapse or progression as post-auto-HSCT consolidation.
• Moskowitz CH, Nademanee A, Masszi T, et al. (2015). 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. The Lancet, May 9;385(9980):1853-62.