Atlanta, GA—Mogamulizumab, a monoclonal antibody targeting CC chemokine receptor type 4 (CCR4), significantly reduced the risk for disease progression or death in patients with untreated cutaneous T-cell lymphoma (CTCL) compared with vorinostat (Zolinza), reported Youn H. Kim, MD, Director, Multidisciplinary Cutaneous Lymphoma Program, Stanford Medicine, California, at ASH 2017.
Patients receiving mogamulizumab had a median progression-free survival (PFS) of 7.7 months versus 3.1 months in patients who received vorinostat. This difference represents a 47% reduction in the hazard ratio for disease progression or death in favor of the anti-CCR4 antibody, stated Dr Kim.
“Mogamulizumab demonstrated convincing clinical activity, not just in skin but also in clearing malignant T-cells in the blood and lymph nodes. PFS and overall global response outcomes are clearly superior,” said Dr Kim. “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,” she added.
The findings came from the randomized, phase 3 clinical trial MAVORIC, which compared mogamulizumab and the histone deacetylase inhibitor, vorinostat, in patients with CTCL who received ≥1 previous systemic regimens. The trial’s key entry criteria mirrored the indication for which the FDA granted priority review to mogamulizumab in November 2017.
The trial involved 372 patients with 1 of 2 predominant subtypes of CTCL—mycosis fungoides or Sézary syndrome. Patients received mogamulizumab 1 mg/kg weekly for 4 weeks and then every 2 weeks thereafter, or vorinostat at a dose of 400 mg daily. Patients allocated to vorinostat could cross over to mogamulizumab at disease progression or in the event of intolerable toxicity. The primary end point was investigator-assessed PFS.
The study population had a median age of 64 to 65 years, and more than 99% of the patients had an Eastern Cooperative Oncology Group performance status 0 or 1. Approximately 67% of the patients had stage III or IV disease. The median number of previous regimens was 3. CCR4 expression level was not included in the eligibility criteria.
The primary analysis yielded a statistically significant hazard ratio of 0.53 in favor of the anti-CCR4 antibody (95% confidence interval [CI], 0.41-0.69; P <.0001). Independent review of the primary end point was consistent with investigator assessment, as patients randomized to mogamulizumab had a median PFS of 6.7 months versus 3.8 months for the vorinostat arm (hazard ratio, 0.64; 95% CI, 0.49-0.84; P = .0007). The advantage for mogamulizumab was consistent across all prespecified subgroups.
The objective response rate was 28% with mogamulizumab and 4.8% with vorinostat (P <.0001). Response rates favored the monoclonal antibody among patients with mycosis fungoides or Sézary syndrome, and among patients with stage III or IV disease. The median duration of response was 14.1 months with mogamulizumab and 9.1 months with vorinostat, and did not vary substantially between patients with mycosis fungoides or Sézary syndrome. Patients who crossed over from vorinostat to mogamulizumab had an objective response rate of 30.1%.
“The response data represent global composite responses in all of the compartments, including skin, lymph nodes, and blood. Responses in all the compartments were integrated into a global response, so the responses were not just in skin,” said Dr Kim.
Grade 1/2 treatment-emergent adverse events occurred in 54.9% of patients treated with the anti-CCR4 antibody, and grade 3/4 adverse events occurred in 42.4%. Treatment-emergent adverse events that occurred substantially more often (>15% difference) with mogamulizumab than with vorinostat were infusion-related reactions (33.2% vs 0.5%, respectively) and skin eruptions (23.9% vs 0.5%, respectively).