Brentuximab Vedotin Approved for the post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation treatment of patients with classical Hodgkin lymphoma (HL) at high risk of relapse or progression
On August 17, 2015, the U. S. Food and Drug Administration approved brentuximab vedotin (ADCETRIS) for the post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation treatment of patients with classical Hodgkin lymphoma (HL) at high risk of relapse or progression.
The approval was based on a randomized, double-blind, placebo controlled clinical trial in 329 patients with classical HL at high risk of relapse or progression based on pre-transplant factors. Following an auto-HSCT, patients were randomized (1:1) to brentuximab vedotin or placebo once every three weeks for a maximum of 16 cycles. The high risk category was defined as one of the following according to status after initial therapy: refractory classical HL, relapsed disease occurring within 12 months, or relapsed disease with extra-nodal involvement. Patients ranged in age from 18-76 years (median 32 years). Patients had received a median of 2 prior systemic therapies (range 2-8) excluding auto-HSCT.
The trial demonstrated a statistically significant improvement in the primary efficacy endpoint of progression free survival (PFS) determined by an independent review facility. The median PFS in the brentuximab vedotin arm was 42.9 months compared to 24.1 months in the placebo arm [Hazard Ratio 0.57 (95% CI 0.40, 0.81; p=0.001)]. At the time of the PFS analysis, an interim analysis of overall survival demonstrated no difference. Patients in the placebo arm could receive ADCETRIS as part of a separate trial after disease progression.
The most common adverse reactions (greater than or equal to 20%) in patients treated with brentuximab vedotin, regardless of causality, were neutropenia, peripheral sensory neuropathy, thrombocytopenia, anemia, upper respiratory tract infection, fatigue, peripheral motor neuropathy, nausea, cough and diarrhea. Twenty-five percent of patients reported serious adverse reactions. The most common serious adverse reactions were pneumonia, pyrexia, vomiting, nausea, hepatotoxicity, and peripheral sensory neuropathy.
Of the patients treated with brentuximab vedotin, infusion-related reactions were reported in 25 patients (15%) and pulmonary toxicity was reported in 8 patients (5%). Any grade of neuropathy was reported in 67%. Of the patients who reported neuropathy, 59% had complete resolution and 41% had residual neuropathy. Adverse reactions leading to dose delays in more than 5% of patients were neutropenia, peripheral sensory neuropathy, upper respiratory tract infection, and peripheral motor neuropathy. Adverse reactions led to treatment discontinuation in 32%. Adverse reactions that led to treatment discontinuation in 2 or more patients were peripheral sensory neuropathy, peripheral motor neuropathy, acute respiratory distress syndrome, paraesthesia and vomiting.
The recommended dose and schedule for brentuximab vedotin as post-auto-HSCT consolidation is 1.8 mg/kg administered intravenously over 30 minutes every 3 weeks. Treatment should be initiated within 4-6 weeks after auto-HSCT or upon recovery from transplantation. The patient should continue treatment until a maximum of 16 cycles, disease progression, or unacceptable toxicity.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).