Low-Dose Alemtuzumab Is Uniquely Effective in Refractory Leukemic Cutaneous T Cell Lymphoma (L-CTCL).

Abstract 3748

Poster Board III-684

Sezary Syndrome and other Cutaneous T Cell Lymphomas with peripheral blood involvement (collectively termed leukemic CTCL, or L-CTCL) are often refractory to multiple therapies. Alemtuzumab, an antibody directed against the pan-lymphocyte antigen CD52, has been used to treat multiple hematologic malignancies, including L-CTCL. However, conventional treatment regimens are associated with an increased risk of infections, and this is of particular concern in CTCL patients with compromised skin integrity. We have treated six L-CTCL patients with a modified regimen of alemtuzumab: 10mg/kg, subcutaneously, three times weekly for six weeks (1/3 of the conventional dose). All patients had had disease for >3 years duration, skin biopsies consistent with CTCL, elevated absolute CD4 counts, CD4/CD8 ratios of >10 and were refractory to at least two prior therapies, including extracorporeal photochemotherapy, interferon, and single and combination agent chemotherapy. In five of six patients, the malignant clone was identifiable using a Vb family specific monoclonal antibody; all cells of the malignant clonotype strongly expressed CD52. Within three weeks, all six patients achieved clearance of detectable T and B cells in peripheral blood, including loss of the malignant clone. In parallel, all patients developed clearing of erythroderma, relief of pruritus, and by the end of the six week treatment period, all patients had complete to near complete resolution of all clinical signs of disease. Isolation of T cells from a skin biopsy of one patient in complete remission revealed that <6% of T cells resident in skin expressed the malignant Vb subunit. At this reduced dose, no infectious complications were encountered. We conclude from that low-dose Aletuzumab is a well tolerated, safe, and highly effective therapy in a carefully selected population of patients with refractory L-CTCL.