Alemtuzumab (Campath-1H) is a humanized monoclonal IgG1k antibody directed against the cell surface antigen CD52; it contains the human variable framework and IgG1 constant regions, and complementarity-determining regions from a murine (rat) monoclonal antibody. Its target, CD52, is a 21-28 kDa cell surface glycoprotein of unknown function found principally on lymphocytes (T & B), as well as monocytes/macrophages, NK cells and granulocytes; it is also expressed in the genital tract. Plasma cells and bone marrow stem cells have little or no CD52. The proposed mechanism of action of alemtuzumab is antibody dependent cellular cytotoxicity (ADCC), although complement dependent lysis and direct apoptosis may also play a role.
Alemtuzumab currently exists under 2 brand names with distinct indications and dosing regimens: Alemtuzumab (Campath) is indicated for intravenous use as a single agent to treat B-cell chronic lymphocytic leukemia (B-CLL). Dosages are escalated to target 90 mg cumulative weekly, for ta total duration of 12 weeks. Alemtuzumab (Campath) was withdrawn from the markets in 2012 by the manufacturer to prepare for a higher-priced relaunch of Lemtrada for the treatment of multiple sclerosis, which was approved by the FDA in November 2014.
Alemtuzumab (Lemtrada) is indicated for adult patients with relapsing-remitting multiple sclerosis with active disease (defined by clinical or imaging features). The recommended dosage is an initial treatment course of intravenous infusion of alemtuzumab 12 mg/day on 5 consecutive days, followed by a second treatment course at the same dosage on 3 consecutive days, 12 months after the initial treatment course, and a recommended safety follow-up of 48 months after the final infusion.
Notable adverse events (based on product monograph and cited references):
- Lymphopenia: Within minutes of infusion, a single dose of alemtuzumab depletes peripheral lymphocyte to undetectable levels. The rate and degree of recovery vary with cell type: B cells recover rapidly after treatment (typically within 3 months after treatment), whereas T cell lymphopenia is prolonged with CD4 and CD8 cells taking 35 and 20 months respectively to reach the lower limit of normal. The lymphopenia is associated with a change in subset composition, with mature naïve B cells (CD19+ CD23+ CD27-) and effector memory T cells dominating upon reconstitution.
- Neutropenia: In previously untreated patients: incidence of grade 3/4 neutropenia was 42%; median time to onset: 31 days; median duration of 37 days. In previously treated patients: incidence of grade 3/4 neutropenia was 64%; median duration of 28 days. 10-17% of neutropenic patients required G-CSF.
- Anemia: In previously untreated patients: incidence of grade 3/4 anemia was 12%; median time to onset: 31 days; median duration of 8 days. In previously treated patients: incidence of grade 3/4 neutropenia was 38%. 17-66% of anemic patients required erythropoiesis-stimulating agents, transfusions, or both.
- Thrombocytopenia: In previously untreated patients: incidence of grade 3/4 thrombocytopenia was 14%; median time to onset: 9 days; median duration of 14 days. In previously treated patients: incidence of grade 3/4 neutropenia was 52%; median duration of 21 days.
- Infections: Patients receiving Alemtuzumab (Campath) are at risk for CMV infection/disease. CMV monitoring via PCR-based method is recommended during therapy and for at least the first 2 months following therapy. Other infections include bacterial (16%), fungal (7%), other viral (4%), or unidentified etiology (76%).
- Infusion reactions, e.g. pyrexia, chills, hypotension, urticarial, dyspnea.
- Autoimmunity (based on published literature): Secondary autoimmune disorders may develop following lymphocyte reconstitution after the use of alemtuzumab. Most commonly, 30% of patients after alemtuzumab develop autoimmune thyroid disease, both Graves’ disease and hypothyroidism. Immune thrombocytopenic purpura (ITP) occurs in 1–3% of patients receiving alemtuzumab.