Phase 2 study of alemtuzumab and dose-adjusted EPOCH-R in relapsed or refractory aggressive B-cell lymphomas.

Abstract

Immune cells within the lymphoma tumor microenvironment promote immune evasion and are rational therapeutic targets. Alemtuzumab targets CD52 expressed on malignant B-cells and infiltrating nonmalignant T-cells. We evaluated the safety and efficacy of alemtuzumab with DA-EPOCH-R in 48 patients with relapsed/refractory aggressive B-cell lymphoma. Febrile neutropenia occurred in 18% of cycles and serious infections in 21% of patients. Responses were observed in 30 (62%) patients, including 12 (80%) patients with classical HL and 3 (75%) patients with T-cell/histiocyte-rich large B-cell lymphoma (THRLCL). Seventeen (35%) patients achieved complete responses, and 12 (25%) were bridged to consolidation. The 2-year progression-free survival (PFS) and overall survival were 22.1% (95% CI, 11.5-34.7%) and 45.2% (95% CI, 34.3-58.9%), respectively. The 2-year PFS for HL and THRLCL patients was 35% and 50%, respectively. Alemtuzumab can be safely combined with DA-EPOCH-R in relapsed/refractory aggressive B-cell lymphomas and can induce durable responses in patients with T-cell-rich microenvironments.