Anti-CCR4 monoclonal antibody KW-0761 (mogamulizumab) or investigator’s choice of chemotherapy in subjects with relapsed or refractory adult T-cell leukemia-lymphoma (ATL).

TPS8622 Background: The receptor for macrophage derived chemokine (MDC) and thymus- and activation-regulated chemokine (TARC) CC chemokine receptor 4 (CCR4) is over expressed in several T-cell malignancies including HTLV-1 related ATL where approximately 90% of malignant cells have been shown to overexpress this chemokine receptor. The HTLV-1 transactivator gene (Tax) does not directly induce CCR4 expression. Rather, expression of CCR4 is controlled by the constitutive activation of several transcription factors in HTLV-1 infected cells. Inhibiting the expression of these transcription factors with small-interfering RNAs has been shown to block CCR4 expression and also reduce proliferation of the affected cells.2 Patients with CCR4 positive ATL are more likely to have skin involvement and shorter overall survival (OS; median 9.5 months) compared with CCR4-negative (20.6 months). Mogamulizumab is a defucosylated, humanized, monoclonal antibody with enhanced antibody-dependent cellular cytotoxicity (Potelli...