The U.S. Food and Drug Administration (FDA) has approved Seattle Genetics’ Adcetris (brentuximab vedotin) for the treatment of adults with the two most common subtypes of cutaneous T-cell lymphoma (CTCL) — non-Hodgkin lymphoma that primarily affects the skin — and who have received prior systemic treatment.
The approval, for patients with either primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF), followed the results of the Phase 3 ALCANZA trial (NCT01578499). Data from two other Phase 2 investigator-sponsored trials also were considered.
Mycosis fungoides and primary cutaneous anaplastic large cell lymphoma are the most common subtypes of CTCL. They can progress from limited skin involvement to skin tumors and ulcers, as well as exfoliation, or the peeling off of layers of skin, which is complicated by itching and infections. Advanced stages involve the lymph nodes, circulating blood, and internal organs.
“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,” Susan Thornton, a cutaneous lymphoma patient and chief executive officer of the Cutaneous Lymphoma Foundation (CLF), said in a press release. “As both a patient and representative of the cutaneous lymphoma community, we welcome the FDA approval of Adcetris as a new treatment option for the most common subtypes of cutaneous T-cell lymphoma in patients who require systemic therapy and we look forward to sharing this important milestone with patients and physicians.”
In the ALCANZA trial, patients receiving Adcetris alone showed significantly higher response rates lasting at least four months compared to patients receiving the standard therapy of methotrexate or bexarotene (56.3% vs. 12.5%, respectively).
Progression-free survival (PFS) ranged from 14.9 months to 22.8 months in Adcetris-treated patients versus 2.4 months to 4.6 months in patients receiving standard care.
The most common adverse reactions were anemia, peripheral sensory neuropathy (numbness, tingling, or pain in the extremities), nausea, diarrhea, fatigue, and low levels of a certain type of white blood cell.
The results of the trial were presented at the 58th American Society of Hematology (ASH) Annual Meeting in December 2016 and published in June 2017 in The Lancet. The study was titled, “Brentuximab vedotin or physician’s choice in CD30-positive cutaneous T-cell lymphoma (ALCANZA): an international, open-label, randomised, phase 3, multicentre trial.”
“These data, along with data from investigator-sponsored clinical trials, led to the FDA approval of Adcetris as a treatment for patients with pcALCL or CD30-expressing MF, which represent the most common subtypes of CTCL,” said Clay Siegall, PhD, president and chief executive officer of Seattle Genetics. “This FDA approval, which was granted more than a month in advance of the PDUFA [Prescription Drug User Fee Act] date, represents a significant milestone for the lymphoma community. Our goal is to establish Adcetris as the foundation of care in CD30-expressing lymphomas.”
This is the fourth FDA-approved indication for Adcetris, which is also approved for patients with relapsed classical Hodgkin lymphoma and relapsed systemic anaplastic large cell lymphoma, and as a consolidation therapy for Hodgkin lymphoma. An approval for its use as a first-line Hodgkin lymphoma therapy in combination with chemotherapy is also pending.