Low-dose intermittent alemtuzumab in the treatment of Sézary syndrome: clinical and immunologic findings in 14 patients.

BACKGROUND AND OBJECTIVES: Alemtuzumab may be effective in Sézary syndrome (SS), an aggressive cutaneous T-cell lymphoma, but is associated with severe hematologic toxicity and infections. This study investigated whether low-dose subcutaneous alemtuzumab can induce hematologic, immunologic, and clinical responses similar to those obtained with the standard regimen, but with less toxicity. DESIGN AND METHODS: Fourteen SS patients were enrolled: 11 had relapsed/refractory disease and three had untreated SS with high counts of circulating Sézary cells (SC). Four received 3 mg alemtuzumab on day 1, 10 mg on day 3, then 15 mg on alternating days; circulating SC were evaluated after the fourth 15 mg dose and treatment was interrupted in the presence of counts <1,000/mm (3). A reduced dosage (3 mg on day 1, then 10 mg on alternating days) was administered to the remaining patients, with SC counted before every injection, until a reduction to values of <1,000/mm (3). RESULTS: The median SC count decreased by 95.5%. Overall, 12/14 patients (85.7%) achieved a clinical response, with three complete responses (21.4%). After a median follow-up of 16 months, the median time-to-treatment failure is 12 months. Infectious complications occurred in 28.6% of patients, all included in the group treated with 15 mg. No patient in the group treated with 10 mg developed hematologic toxicity or infections. An early recovery of circulating NK, B and CD3+CD8+ cells occurred after the first cycle. INTERPRETATION AND CONCLUSIONS: Subcutaneous alemtuzumab at very low doses (10 mg maximum per administration), given for a short period based on SC levels, has a good toxicity profile, high response rate and causes durable remissions in SS patients with high tumor burden in the peripheral blood.