Cutaneous T-cell lymphomas (CTCLs) are uncommon cancers that mostly affect the skin. In advanced CTCL, therapeutic responses are typically transient. The factors that influence long-term CTCL control remained unknown. Mogamulizumab, an anti-human CCR4 antibody that inhibits CCR4+ CTCL tumor cells and peripheral memory blood regulatory T cells via antibody-dependent cell cytotoxicity, has been linked to long-term remissions and immunological side effects. Skin rashes were detected in 32% of 44 CTCL patients treated with mogamulizumab, and they were related to significantly better overall survival (hazard ratio, 0.16; 0.04-0.73; P =.01). Rash developed in Sézary syndrome patients and was related to a longer time to progression. A CD163+ granulomatous and/or CD8+ lichenoid cutaneous infiltration characterized these rashes. High-throughput sequencing of T-cell receptor genes in skin and blood flow cytometry revealed CTCL tumor cell reduction as well as the recruitment of novel reactive T-cell clones in the skin during skin rash.
CXCL9 and CXCL11, two chemokines generated from macrophages that attract CXCR3+ T lymphocytes to the skin, were shown to be overexpressed in skin rashes. Patients with a rash had a greater frequency of TIGIT+ and PD1+ exhausted reactive blood T cells at baseline, which was reduced with mogamulizumab therapy. The findings supported mogamulizumab-induced long-term immunological CTCL control via activation of macrophage and T-cell responses in patients with rash.
