FDA Approves Mogamulizumab for CTCL

The FDA has approved mogamulizumab-kpkc (Poteligeo) for the treatment of patients with cutaneous T-cell lymphoma (CTCL) who have received at least 1 prior systemic therapy.

The approval is specifically for patients with mycosis fungoides (MF) or Sézary syndrome (SS), 2 subtypes of CTCL. The FDA based its decision on findings from the phase III MAVORIC study. Results from the study presented at the 2017 ASH Annual Meeting showed that mogamulizumab reduced the risk of progression or death by 47% compared with vorinostat (Zolinza) in previously treated patients with CTCL.

"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.”

The MAVORIC study included 372 patients with histologically confirmed stage IB to IVB MF or SS who had failed ≥1 systemic therapy. Patients were evenly randomized to 1.0 mg/kg of mogamulizumab weekly for the first 4-week cycle and then every 2 weeks, or vorinostat at 400 mg daily. Crossover to mogamulizumab was allowed for patients receiving vorinostat who progressed or had intolerable toxicity. PFS was the primary endpoint.

Patient characteristics were similar between the 2 arms. These included age (median, 63.5 vs 65 years in the mogamulizumab vs vorinostat arms, respectively), ECOG performance status of 0 or 1 (99% vs 100%), and stage III/IV disease (63.4% vs 61.3%). In both arms, the median number of prior systemic therapies was 3. CCR4 expression level was not an eligibility criteria.

The investigator-assessed median PFS was 7.7 months (95% CI, 5.7-10.3) in the mogamulizumab arm compared with 3.1 months (95% CI, 2.9-4.1) in the vorinostat arm (HR, 0.53; 95% CI, 0.41-0.69; P <.0001). By independent review, the median PFS was 6.7 versus 3.8 months, respectively (HR, 0.64; 95% CI, 0.49-0.84; P = .0007). The PFS benefit with mogamulizumab was observed across predefined subgroups, including disease type and disease stage.

The overall response rate (ORR) was 28% with mogamulizumab versus 4.8% with vorinostat (P <.0001). Among patients with MF and SS, the ORR was 21.0% vs 7.1% (P = .0042) and 37.0% vs 2.3% (P <.0001), respectively. Mogamulizumab also improved ORR in patients with stage III disease at 22.7% versus 0, and stage IV disease at 36.5% versus 3.1%. Among patients assigned to vorinostat who crossed over to mogamulizumab, the ORR was 30.1%

Grade 1/2 treatment-emergent adverse events (TEAEs) were experienced by 54.9% of patients receiving mogamulizumab, with 42.4% of patients experiencing grade 3 to 5 TEAEs.

TEAEs occurring in more than 20% of patients that were more common with mogamulizumab versus vorinostat included infusion-related reactions (33.2% vs 0.5%) and skin eruptions due to drug (23.9% vs 0.5%).

TEAEs more common with vorinostat versus mogamulizumab included diarrhea (61.8% vs 23.4%), nausea (42.5% vs 15.2%), thrombocytopenia (30.6% vs 11.4%), dysgeusia (29.0% vs 3.3%), and increased blood creatinine (28.0% vs 3.3%).

Kim YH, MD, Bagot M, Pinter-Brown L et al. Anti-CCR4 monoclonal antibody, mogamulizumab, demonstrates significant improvement in PFS compared to vorinostat in patients with previously treated cutaneous T-Cell lymphoma (CTCL): results from the phase III MAVORIC study. Abstract available ahead of 2017 ASH Annual Meeting; December 9-12, 2017; Atlanta, GA. Abstract 817.