Immunological Status Affects Efficacy of Mogamulizumab in ATL, Study Finds

A new study helps explain immunological factors that appear to have an impact on the success rate of mogamulizumab in patients with adult T-cell leukemia-lymphoma (ATL).

Mogamulizumab (Poteligio) causes meaningful anticancer activity in adult T-cell leukemia-lymphoma (ATL), but the outcomes of therapy are highly dependent on the patient’s immunological status prior to treatment, according to a new study.

Mogamulizumab has been approved in the United States to treat relapsed/refractory ATL since 2012, and Japan approved the drug to treat newly diagnosed ATL in 2014.

A defucosylated humanized antibody, mogamulizumab works by targeting CCR4+ cells by enhanced antibody-dependent cellular cytotoxicity. CCR4 is expressed by the tumor cells of most patients with ATL and some patients with peripheral T-cell lymphoma.

Writing in the journal Blood Advances, corresponding author Takashi Ishida, MD, PhD, of the Nagoya City University Graduate School of Medical Sciences, in Japan, and colleagues noted that the drug has been associated with severe skin disorders or viral infections in some patients.

“On the other hand, quite puzzlingly, moderate skin-related [adverse events] after mogamulizumab were associated with a favorable prognosis,” the investigators wrote.

The theory is that these adverse events (AEs) were associated with the depletion of CCR4+ cells, and regulatory T cells in particular, Ishida and colleagues said. However, data on immune alterations as a result of the therapy are not yet available. The investigators therefore sought to explore prospectively how the drug affected clinical and immunological parameters of mogamulizumab-naive patients, and what relationship those changes had on treatment outcomes.

The multicenter trial enrolled 102 mogamulizumab-naive patients, all but one of whom would go on to receive mogamulizumab-containing treatment. The subtypes were as follows: 68 acute, 18 lymphoma, 12 chronic, and 3 smoldering.

“At enrollment, there was a significant inverse correlation between serum soluble interleukin-2 receptor (sIL-2R) levels and percentages of Tax-specific cytotoxic T lymphocytes (Tax-CTLs) in the entire lymphocyte population or in the CD81 T cell subset, but there was not a correlation with cytomegalovirus pp65–specific cytotoxic T lymphocytes (CMV-CTLs),” the investigators said.

Nearly two-thirds (65%) of patients responded to treatment. Median progression-free survival (PFS) was 7.4 months, and overall survival (OS) was 16.0 months.

Ishida and colleagues found that patients with a higher percentage of Tax-CTLs, but not CMV-CTLs, within the entire lymphocyte population or within the CD8+ T-cell subset had longer survival, on average.

A multivariate analysis further showed that acute or lymphoma subtype, a higher sIL-2R level, and a lower percentage of CD2-CD19+ B cells in peripheral blood mononuclear cells were independent predictors of an unfavorable prognosis for overall survival.

“This indicates that a higher percentage of B cells might reflect some aspect of a favorable immune status leading to a good outcome with mogamulizumab treatment,” the authors wrote.

Ishida and colleagues noted that while their findings generally align with established unfavorable prognostic factors, the current study did not indicate that old age necessarily leads to a negative prognosis, a finding that differs from earlier research.

The authors noted a number of limitations. First, the study included both previously treated and untreated patients, and the prior treatments of some patients could have had an effect on their immunological status prior to receiving mogamulizumab. Additionally, the patients in the study received various mogamulizumab-containing treatments, and some received mogamulizumab monotherapy, factors that could also affect the outcomes observed.

Ishida and colleagues said further research should include further time series analysis and comprehensive genomic analyses.

Reference

Yonekura K, Kusumoto S, Choi I, et al. Mogamulizumab for adult T-cell leukemia-lymphoma: a multicenter prospective observational study. Blood Adv. 2020;4(20):5133-5145. doi:10.1182/bloodadvances.2020003053