The United States Food and Drug Administration has announced the approval of mogamulizumab (Poteligeo) for the intravenous treatment of adult patients with mycosis fungoides and Sézary syndrome, two subtypes of cutaneous T-cell lymphoma (CTCL), a rare non-melanoma skin cancer. Mogamulizumab is indicated for relapsed or refractory mycosis fungoides or Sézary syndrome following at least one prior systemic therapy.
The approval was based on the results of the MAVORIC trial, the largest randomized trial of mycosis fungoides and Sézary syndrome to date and the first clinical trial to examine progression-free survival as a primary outcome. MAVORIC was a phase III, open-label, multicenter, randomized trial comparing the efficacy of mogamulizumab versus vorinostat in 372 patients with mycosis fungoides or Sézary syndrome who had previously failed at least one prior systemic treatment.
Median progression-free survival was 7.6 months with mogamulizumab (95% CI, 5.6-10.2) versus 3.1 months with vorinostat (95% CI, 2.8-4.0). Furthermore, overall response rate for patients who received mogamulizumab was 28% compared with 5% for those treated with vorinostat (P < .001).
"Mycosis fungoides (MF) and Sézary syndrome (SS) can be disfiguring and debilitating. MAVORIC showed that mogamulizumab prolonged progression-free survival compared to vorinostat in patients with relapsed or refractory MF or SS," stated Jeffrey S. Humphrey, MD, president of Kyowa Kirin Pharmaceutical Development, Inc.
CTCL is often misdiagnosed as other less serious skin lesions, which delays proper treatment. Mycosis fungoides is a slowly progressive form of lymphoma and the most frequent subtype of CTCL, representing between 50% and 70% of CTCL cases. Sézary syndrome is a more aggressive, leukemic form of CTCL and represents 3% of CTCL cases.
Mogamulizumab is a monoclonal antibody that targets the CC chemokine receptor 4 (CCR4). This receptor is expressed in certain blood cancers, including CTCL. Researchers used proprietary technology to decrease the amount of fucose in mogamulizumab’s sugar chain, thus improving the drug’s antibody-dependent cellular toxicity.
The most common adverse reactions associated with mogamulizumab include rash, infusion reaction, fatigue, diarrhea, drug eruption, upper respiratory tract infection, musculoskeletal pain, skin infection, pyrexia, edema, nausea, headache, thrombocytopenia, constipation, anemia, mucositis, cough, and hypertension. Such reactions were reported in ≥10% of patients in the MAVORIC clinical trial.
Clinicians should monitor patients administered mogamulizumab for dermatologic toxicity and rash. If a moderate or severe rash occurs, treatment should be interrupted; however, if a life-threatening rash, Stevens-Johnson syndrome, or toxic epidermal necrolysis occur, the drug should be permanently discontinued.
Additional monitoring for infusion reactions, infections, autoimmune complications, and transplant complications should also be completed. Mogamulizumab administration should be interrupted if any grade infusion reaction occurs, and patients who experience life-threatening infusion reactions should discontinue treatment with the drug.
“Mycosis fungoides and Sézary syndrome are rare, hard-to-treat types of non-Hodgkin lymphoma and this approval fills an unmet medical need for these patients,” said Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “We are committed to continuing to expedite the development and review of this type of targeted therapy that offers meaningful treatments for patients.”