The US Food and Drug Administration (FDA) today approved brentuximab vedotin (Adcetris, Seattle Genetics and Takeda) for the treatment of patients with cutaneous T-cell lymphoma (CTCL) who have received prior systemic therapy.
Specifically, it was approved for patients with primary cutaneous anaplastic large cell lymphoma or CD30-expressing mycosis fungoides, which are the most common subtypes of CTCL.
Brentuximab vedotin is an antibody-drug conjugate that targets CD30, which is a defining marker of classic Hodgkin lymphoma. It is composed of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a cytotoxic agent, monomethyl auristatin E.
Approval was based on results from the phase 3 randomized clinical trial (ALCANZA) wherein 56% of patients treated with brentuximab had an objective response lasting at least 4 months compared with 12% of those treated with physician’s choice (methotrexate or bexarotene; P < .001). This was the study’s primary endpoint.
In terms of secondary endpoints, brentuximab was also superior to physician’s choice for complete responses (16% vs 2%; P = .007) and progression-free survival (median, 17 vs 4 months; hazard ratio, 0.27; P < .001).
Data from ALCANZA were reported last year at the annual meeting of the American Society of Hematology.
At that time, Stephanie Lee, MD, MPH, professor of medicine at the University of Washington in Seattle, who was not involved in the study, said, “This trial shows that brentuximab vedotin has significant advantages over two commonly used treatments for this disease.”
In the trial, investigators randomly assigned 131 patients to brentuximab vedotin 1.8 mg/kg intravenously, once every 3 weeks, or physician’s choice of methotrexate 5 to 50 mg orally, once weekly, or bexarotene 300 mg/m² (target dose) orally, once daily, for up to 48 weeks (16 cycles), until disease progression or unacceptable toxicity.
At the ASH meeting last year, investigators said that safety data were consistent with the established tolerability profile for brentuximab vedotin, which has multiple other blood cancer indications. They also reported that drug-related grade 3/4 adverse events were observed in 29% of patients in both treatment groups.
The rate of peripheral sensory neuropathy of any grade, however, was much higher with brentuximab than with standard care (67% vs 6%). The most common adverse event leading to discontinuation was peripheral neuropathy, according to the FDA.
The agency also said that the other most common adverse reactions, occurring in more than 20% of patients receiving brentuximab vedotin, were anemia, nausea, diarrhea, fatigue, and neutropenia.
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