ASH 2017: Targeted Antibody Mogamulizumab Superior to Vorinostat for Previously Treated CTCL in Phase III Trial
In a large, international, randomized phase III trial presented by Kim et al at the 59th American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 817), patients with previously treated cutaneous T-cell lymphoma (CTCL) who received the investigational targeted drug mogamulizumab had significantly better progression-free survival, response rate, and quality of life than patients who received vorinostat (Zolinza), a U.S. Food and Drug Administration (FDA)-approved standard-of-care treatment for patients with CTCL. The adverse events observed with mogamulizumab treatment were generally mild to moderate in severity.
CTCL is a rare cancer of the white blood cells—specifically, T lymphocytes—that primarily occurs in the skin. CTCL can also involve the blood, lymph nodes, and internal organs.
Mogamulizumab targets the CCR4 protein, which is frequently found on the surface of cancer cells in patients with CTCL. As a CCR4 antibody, the drug exploits the patient’s immune cells to attack the cancer.
Vorinostat, one of several drugs approved by the FDA to treat CTCL, works by blocking the action of an enzyme that helps cancerous T cells survive and multiply.
Study Findings
The primary endpoint of the phase III trial was progression-free survival or death for any reason.
Among 372 patients included in the trial, the median progression-free survival was 7.7 months for patients treated with mogamulizumab compared with 3.1 months for those treated with vorinostat, reported lead study author Youn H. Kim, MD, Professor of Dermatology and Director of the Multidisciplinary Cutaneous Lymphoma Program at the Stanford University School of Medicine.
Adverse effects such as diarrhea, nausea, altered taste, decreased appetite, increased blood creatinine levels, and decreased platelet counts occurred more than twice as frequently in patients treated with vorinostat than in those treated with mogamulizumab, said Dr. Kim. By contrast, the adverse effects seen most frequently in patients treated with mogamulizumab were drug rash and infusion-related reactions, such as chills and flushing.
Mogamulizumab was administered as a once-weekly intravenous infusion for the first 28-day cycle and every 2 weeks during subsequent cycles. Vorinostat was taken as a once-daily pill.
Dr. Kim said the next step will be to learn more about biomarkers that can predict treatment outcome and to test whether clinical benefit can be further improved by combining mogamulizumab with skin-directed or other systemic therapies that have different mechanisms of action.
“We found that mogamulizumab has convincing clinical activity, not just in skin, but also in clearing malignant T cells in the blood and lymph nodes,” said Dr. Kim. “Progression-free survival and overall global response outcomes are clearly superior, the side effects are tolerable, and we see measurable improvements in quality of life with mogamulizumab compared with vorinostat. Taken together, these findings represent a durable and clinically meaningful benefit for patients with CTCL.”
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