TCL-194: Change in Lymphocyte Count as a Predictor of Response to Mogamulizumab in Patients with Mycosis Fungoides or Sézary Syndrome

Abstract

Context Mogamulizumab is an anti-CCR4 antibody for patients with relapsed/refractory mycosis fungoides (MF) or Sezary syndrome (SS). The mechanism of action of mogamulizumab involves depletion of CCR4+ T cells and potential to induce lymphopenia. Objective This post hoc analysis of the phase 3 MAVORIC study evaluated the shift in lymphocyte populations during therapy and correlated changes from baseline to highest grade of lymphopenia with clinical outcomes. Design MAVORIC patients received mogamulizumab (1.0 mg/kg IV weekly for 4 weeks, then biweekly; n=186) or vorinostat (400 mg/d PO; n=186). Patients were stratified by baseline blood involvement (B0, B1, B2). Changes in cell types (absolute counts of CD8+CD3+/-, CD4+CD26-, CD4+CD7-, and CD4/CD8 ratio) were assessed. Response was determined using global composite response, as well as separately within skin. Results Grade 1–4 lymphopenia occurred in 80% (138/174) of mogamulizumab patients. Shifts from grade 0 at baseline to 1 during therapy occurred in 6% of patients, grade 0 to 2–3 in 47%, and grade 0 to 4 in 6%. Infections/infestations after a reduction in absolute lymphocyte count were reported in 18 (11.3%), 53 (33.3%), 22 (13.8%), or 5 (3.2%) of patients with grade 1, 2, 3, or ≥4 lymphopenia, respectively. Blood involvement (B1=detectable Sezary cells Conclusions Mogamulizumab induced early and sustained lymphopenia. No increase in the incidence of infections with severity of lymphopenia was observed. There was no correlation with the depth of lymphopenia and clinical response, but patients with advanced disease and circulating Sezary cells had higher grade lymphopenia, reflecting mogamulizumab’s effect on clearing CCR4-expressing Sezary cells from blood. Depth of lymphopenia in mogamulizumab-treated patients did not correlate with clinical response, but early change in CD4+/CD8+ may be a biomarker for eventual skin response. Supported by Kyowa Kirin, Inc.