Youn H. Kim, MD

The anti-CCR4 monoclonal antibody mogamulizumab may answer an unmet need in providing an effective treatment of cutaneous T-cell lymphoma. In the phase III MAVORIC trial reported at the 2017 American Society of Hematology (ASH) Annual Meeting & Exposition, treatment with mogamulizumab was associated with a doubling in median progression-free survival time, compared with vorinostat (Zolinza), in previously treated patients with cutaneous T-cell lymphoma.¹

MAVORIC, which enrolled 372 patients, is reportedly the largest randomized trial in cutaneous T-cell lymphoma and the first pivotal trial to use progression-free survival as a primary endpoint and to incorporate the consensus comprehensive global response criteria. Treatment with mogamulizumab resulted in a median progression-free survival of 7.7 months, vs 3.1 months with vorinostat, translating into a 47% reduction in risk (P < .0001), reported Youn H. Kim, MD, Professor of Dermatology and Director of the Multidisciplinary Cutaneous Lymphoma Program at Stanford University School of Medicine.

“Mogamulizumab demonstrated significantly superior efficacy outcomes compared to vorinostat in patients with previously treated cutaneous T-cell lymphoma,” Dr. Kim said. “This study supports mogamulizumab as a valuable new therapeutic option in these patients.”

Mogamulizumab is a humanized monoclonal antibody directed against C-C chemokine receptor type 4 (CCR4), which is frequently expressed in certain hematologic malignancies, including cutaneous T-cell lymphoma. The drug is already approved for adult T-cell leukemia/lymphoma in Japan. Mogamulizumab has received Breakthrough Therapy designation for both mycosis fungoides and Sézary syndrome in adults who have received at least one prior systemic therapy.²

MAVORIC Details

The MAVORIC trial was conducted in 59 centers across 11 countries, enrolling 373 patients with mycosis fungoides or Sézary syndrome (stages IB–IVB) who had failed to respond to one or more systemic therapies. Patients were randomized to receive either mogamulizumab at 1.0 mg/kg (weekly for the first 4-week cycle, then every 2 weeks) or vorinostat at 400 mg daily. The vorinostat-treated patients could cross over to mogamulizumab treatment upon disease progression.

The primary endpoint was investigator-assessed progression-free survival using the global composite response, which is based on skin, blood, nodes, and viscera. Risk for this endpoint was reduced by 47%, a finding that was verified by an independent review showing median progression-free survival to be 6.7 vs 3.8 months (hazard ratio = 0.64; P = .0007). Superior progression-free survival was seen across all prespecified subgroups.

Mogamulizumab also significantly improved response rates overall (28% vs 5%; P < .0001), in patients with mycosis fungoides (21% vs 7%; P = .0042) and in patients with Sézary syndrome (37% vs 2%; P < .0001). Thirty percent of control-group patients who crossed over achieved a response. The median duration of response was 14 vs 9 months, respectively.

Quality of Life

Statistically significant improvements in patient-reported quality of life were also observed with mogamulizumab, based on Skindex-29 symptoms scale (for cycles 3, 5, and 7; P < .05), the Functional Assessment of Cancer Therapy–General Functional Well-Being scale (for cycles 3, 5, 7, and 9; P = .05), and other instruments.

Commenting at the press briefing on the drug’s impact on patients, Dr. Kim described cutaneous T-cell lymphoma as a “unique disease that you can see and feel” and one in which the associated itching is so severe “patients cannot sleep or function.” The Skindex-29 scale measures the physical and psychosocial impact of cutaneous T-cell lymphoma on symptoms and quality of life. “We intensively looked at these things and showed a significant improvement over the vorinostat comparator, which also produced quality-of-life improvements, but the improvement with mogamulizumab was more objective.” ■

DISCLOSURE: Dr. Kim has received research funding from Eisai, Millennium Pharmaceuticals, Soligenix, Seattle Genetics, Portola, Neumedicine, miRagen, Merck, Kyowa-Kirin-Pharma, Innate Pharma, Horizon Pharma, Forty Seven Inc, and Tetralogic. He also has served as an advisor or consultant to Eisai, Seattle Genetics, Portola, Medivir, Kyowa-Kirin-Pharma, Innate Pharma, Horizon Pharma, Forty Seven Inc, and Millennium Pharmaceuticals.

REFERENCES

1. Kim YH, Bagot M, Pinter-Brown L, et al: Anti-CCR4 antibody, mogamulizu-mab, demonstrates significant improvement in PFS compared to vorinostat in patients with previously treated cutaneous T-cell lymphoma. 2017 ASH Annual Meeting. Abstract 817. Presented December 11, 2017.

2. Winsett F, Ni X, Duvic M: Mogamulizumab in the treatment of cutaneous T cell lymphoma. Exp Opin Orphan Drugs 4:1277-1280, 2016.