Mogamulizumab reduced the number of HTLV-1–infected cells and levels of inflammatory markers in patients with HTLV-1–associated myelopathy–tropical spastic paraparesis (HAM-TSP) in a recently reported phase 1-2a study.
Treatment with the anti-CCR4 monoclonal antibody also reduced spasticity and motor disability in some patients with HAM-TSP, according to resultsin the New England Journal of Medicine.
Rash was the main side effect of treatment, but the 21-patient trial was “too small and too short to evaluate the clinical safety of mogamulizumab,” said lead author Tomoo Sato, MD, PhD, of the Department of Rare Diseases Research, St. Marianna University, Kawasaki, Japan, and colleagues.
HAM-TSP is a chronic, progressive, and debilitating neuroinflammatory disorder primarily seen in equatorial regions, according to.
HTVL-1 infects primarily CCR4+ T cells, and mogamulizumab is an anti-CCR4 antibody that targets those affected cells, according to Dr. Sato and colleagues.
Current treatment for HAM-TSP is typically focused on suppressing inflammation with glucocorticoid or interferon-alpha rather than attacking infected cells and reducing proviral load.
The current investigator-initiated study included 21 patients with glucocorticoid-refractory HAM-TSP. In phase 1 of the study, patients received a single intravenous infusion of mogamulizumab and were observed for 85 days. Of those patients, 19 continued to phase 2a and received infusions at 8- or 12-week intervals for a total of 24 weeks.
Treatment resulted in a reduction of 64.9% (95% confidence interval, 51.7-78.1) in proviral load in peripheral-blood mononuclear cells by day 15 postinfusion. Reductions in inflammatory markers at day 29 were also reported, including a 37.3% decrease in CXCL10 levels and a 21.0% decrease in neopterin levels.
In all, 79% of patients had a reduction in spasticity, and 32% had decreased motor disability after treatment.
“The clinical effects appeared very quickly, long before any changes in the markers of inflammation in the central nervous system,” the investigators said.
Grade 1 or 2 rash was seen in 48% of patients, while lymphopenia and leukopenia were seen in 33% of patients each.
A phase 2 study is ongoing to evaluate the long-term safety and efficacy of mogamulizumab in patients with HAM-TSP.
The study was supported by the Japan Agency for Medical Research and Development and by the Ministry of Health, Labor, and Welfare. Two of the coauthors reported patents related to treating HTLV-I–related myelopathy.
SOURCE: Sato T et al. .