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.
"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," commented Susan Thornton, who has cutaneous lymphoma and is chief executive officer of the Cutaneous Lymphoma Foundation. "As both a patient and representative of the cutaneous lymphoma community, we welcome the…new treatment option," she said in a statement
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.
This is the fourth FDA-approved indication for brentuximab vedotin. It already has regular approval for use in patients with classic Hodgkin lymphoma (cHL) in whom autologous hematopoietic stem cell transplantation (auto-HSCT) has failed or at least two prior multiagent chemotherapy regimens have failed and who are not candidates for auto-HSCT, as well as in patients with cHL who are at high risk for relapse or progression as post–auto-HSCT consolidation. In addition, the drug has an accelerated approval for treatment of patients with systemic anaplastic large cell lymphoma in whom at least one prior multiagent chemotherapy regimen has failed.
The latest approval, for use in CTCL, is a regular (not accelerated) approval. It was based on results from the phase 3 randomized clinical trial ALCANZA, which showed that brentuximab vedotin "demonstrated superior efficacy with durable responses for long-term disease management when compared to standard of care treatment options methotrexate and bexarotene," according to the company.
In that trial, 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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Cite this: FDA Approves Brentuximab for Cutaneous T-Cell Lymphoma - Medscape - Nov 09, 2017.