Campath-1H (anti-CD52) monoclonal antibody therapy in lymphoproliferative disorders.
Campath-1H is a humanized monoclonal antibody targeted against the CDw52 membrane antigen of lymphocytes, which causes complement and antibody-dependent cell-mediated cytotoxicity. Campath-1H has been used in B-chronic lymphocytic leukemia (B-CLL), T-prolymphocytic leukemia (T-PLL), and low-grade non-Hodgkin's lymphoma (LGNHL). Campath-1H is administered intravenously thrice weekly for up to 12 wk, at an initial dose of 3 mg, escalated to 10 and 30 mg. The responses (complete [CR] and partial [PR]) obtained in untreated B-CLL patients are of the order of 90%. In previously treated B-CLL patients, responses are of the order of approximately 40%, with 2-4% CRs. Responses are more prominent in the blood and bone marrow compared to the lymph nodes. 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 purging of residual disease in B-CLL, followed by autologous stem-cell transplantation. In heavily pretreated advanced stage LGNHL, response is achieved only in 14% of cases with B-phenotype; a 50% response rate is noted in mycosis fungoides. In T-PLL, the CR rate is approximately 60%. Promising results have been reported in a small number of patients with refractory autoimmune thrombocytopenia of lymphoproliferative disorders. The main complications of Campath-1H treatment are caused by tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 release, usually during the first intravenous infusion, and include fever, rigor, nausea, vomiting, and hypotension responsive to steroids. These side effects are usually less severe with subsequent infusions and can be prevented by paracetamol and antihistamines. Immunosupression resulting from normal B- and T-lymphocyte depletion is frequent, resulting in an increased risk for opportunistic infections. More clinical trials in a larger number of patients are necessary to determine the exact role and indications of Campath-1H in lymphoproliferative disorders.
Pangalis
G A
GA
1st Department of Internal Medicine, National and Kapodistrian University of Athens, Laikon General Hospital, Greece. pangalis@otenet.gr
Dimopoulou
M N
MN
Angelopoulou
M K
MK
Tsekouras
C
C
Vassilakopoulos
T P
TP
Vaiopoulos
G
G
Siakantaris
M P
MP
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007165:Immunosuppression Therapy; D007239:Infections; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000009:adverse effects / Q000378:metabolism; D015448:Leukemia, B-Cell / Q000188:drug therapy*; D015463:Leukemia, Prolymphocytic / Q000188:drug therapy*; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D010641:Phenotype; D012307:Risk Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000009:adverse effects / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000074323:Alemtuzumab