The FDA has approved brentuximab vedotin (Adcetris, Seattle Genetics, Inc.) for the treatment of adults with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF)––the most common subtypes of cutaneous T-cell lymphoma––who have received prior systemic therapy.
Approval was based on a phase 3, randomized, open-label, multicenter clinical trial (ALCANZA) of brentuximab vedotin in patients with MF or pcALCL who had previously received one prior systemic therapy and required systemic treatment. The trial randomized 131 patients (1:1) to receive either brentuximab vedotin or the physician’s choice of methotrexate or bexarotene.
Efficacy was established based on improvement in objective response rate lasting four months (ORR4), complete response (CR) rate, and progression-free survival (PFS) assessed by an independent review facility. ALCANZA demonstrated an improvement (P < 0.001) in ORR4 in the brentuximab vedotin arm versus the physician’s choice arm: 56% (95% confidence interval [CI], 44%–68%) versus 12% (95% CI, 4%–21%), respectively.
CR rate was also superior (P = 0.007) in the brentuximab vedotin arm versus the physician’s choice arm: 16% (95% CI, 8%–27%) versus 2% (95% CI, 0–8%). ALCANZA also demonstrated improvement in PFS with an estimated hazard ratio of 0.27 (95% CI, 0.17–0.43; P < 0.001). The median PFS was 17 months in the brentuximab vedotin arm versus four months in the physician’s choice arm.
The most common adverse reactions occurring in more than 20% of patients receiving brentuximab vedotin were anemia, peripheral sensory neuropathy, nausea, diarrhea, fatigue, and neutropenia. The most common adverse event leading to discontinuation was peripheral neuropathy.
“Cutaneous T-cell lymphoma is a blood cancer of the skin with no known cure and few new treatment options. It is a disfiguring disease in dire need of more effective and durable treatment options to help keep this debilitating and painful disease at bay,” said Susan Thornton, a cutaneous lymphoma patient and chief executive officer of the Cutaneous Lymphoma Foundation.
The recommended dose of brentuximab vedotin is 1.8 mg/kg up to a maximum of 180 mg as an intravenous infusion over 30 minutes every three weeks until a maximum of 16 cycles, disease progression, or unacceptable toxicity.
The new indication (which received regular approval) is the fourth FDA-approved indication for Adcetris, which also has 1) regular approval for treatment of classical Hodgkin’s lymphoma (cHL) patients who fail autologous hematopoietic stem cell transplantation (auto-HSCT) or who fail at least two prior multiagent chemotherapy regimens and are not auto-HSCT candidates; 2) regular approval for the treatment of patients with cHL at high risk of relapse or progression as post-auto-HSCT consolidation; and 3) accelerated approval for treatment of systemic anaplastic large cell lymphoma (sALCL) patients who fail at least one prior multiagent chemotherapy regimen.
Accelerated approval in the sALCL indication is based on overall response rate, and continued approval may be contingent upon verification of clinical benefit in confirmatory trials.
The FDA granted breakthrough therapy, orphan drug, and priority review designations to brentuximab vedotin for this indication.