Alemtuzumab.
Alemtuzumab is an unconjugated, humanised, monoclonal antibody directed against the cell surface antigen CD52 on lymphocytes and monocytes. In noncomparative phase I/II studies in patients with B-cell chronic lymphocytic leukaemia (B-CLL) relapsed after or refractory to alkylating agents and fludarabine, intravenous (IV) administration of alemtuzumab 30 mg/day three times weekly for up to 12 weeks was associated with overall objective response (OR) rates of 21-59%. Combining alemtuzumab with fludarabine resulted in ORs >80%. In noncomparative studies in patients with previously untreated B-CLL, subcutaneous (SC) administration of alemtuzumab alone, or IV in combination with fludarabine, was highly effective, achieving OR rates of around 90%. IV alemtuzumab was active in patients with chemotherapy-resistant/relapsed T-cell prolymphocytic leukaemia, with reported OR rates of 24-76%. Alemtuzumab has been incorporated in novel conditioning regimens designed to facilitate stem cell transplantation in haematological malignancies. Adverse events with alemtuzumab are predictable and manageable. 'First-dose' flulike symptoms, frequently seen after IV infusion, can be managed by (pre)medication and minimised by dose escalation (or SC injection). Anti-infective prophylaxis is mandatory. Cytopenias are transient, although red blood cell and platelet support may be required.
Frampton
James E
JE
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz
Wagstaff
Antona J
AJ
D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D015448:Leukemia, B-Cell / Q000145:classification / Q000188:drug therapy* / Q000628:therapy; D008657:Metabolic Clearance Rate
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000970:Antineoplastic Agents; D000074323:Alemtuzumab