Campath-1H (anti-CD52) monoclonal antibody therapy in lymphoproliferative disorders - A review

Campath-1H is a humanized monoclonal antibody targeted against the CDw52 me mbrane antigen of lymphocytes, which causes complement and antibody-depende nt cell-mediated cytotoxicity. Campath-1H has been used in B-chronic lympho cytic leukemia (B-CLL), T-prolymphocytic leukemia (T-PLL), and low-grade no n-Hodgkin's lymphoma (LGNHL). Campath-1H is administered intravenously thri ce weekly for up to 12 wk, at an initial dose of 3 mg, escalated to 10 and 30 mg. The responses (complete FCR] and partial [PR]) obtained in untreated B-CLL patients are of the order of 90%. In previously treated B-CLL patien ts, responses are of the order of approximately 40%, with 2-4% CRs. Respons es are more prominent in the blood and bone marrow compared to the lymph no des. The median duration of response is 9-12 mo. Because of the antibody's higher activity on circulating lymphocytes, it has been used for in vivo pu rging of residual disease in B-CLL, followed by autologous stem-cell transp lantation. In heavily pretreated advanced stage LGNHL, response is achieved only in 14% of cases with B-phenotype; a 50% response rate is noted in myc osis fungoides. In T-PLL, the CR rate is approximately 60%. Promising resul ts have been reported in a small number of patients with refractory autoimm une thrombocytopenia of lymphoproliferative disorders. The main complicatio ns of Campath-1H treatment are caused by tumor necrosis factor (TNF)-alpha, and interleukin (IL)-6 release, usually during the first intravenous infus ion, and include fever, rigor, nausea, vomiting, and hypotension responsive to steroids. These side effects are usually less severe with subsequent in fusions and can be prevented by paracetamol and antihistamines. Immunosupre ssion resulting from normal B- and T-lymphocyte depletion is frequent, resu lting in an increased risk for opportunistic infections. More clinical tria ls in a larger number of patients are necessary to determine the exact role and indications of Campath-1H in lymphoproliferative disorders.