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Alemtuzumab is a genetically engineered chimeric murine/human monoclonal antibody against the glycoprotein CD 52 situated at the surface of lymphocytes.

CD52 protein is usually expressed at the surface of normal and malignant peripheral blood B and T lymphocytes as well as monocytes, thymocytes and macrophages. The antigen is also slightly present (< 5%) on the granulocyte surface but not on erythrocytes or platelets.

Alemtuzumab does not perturb haematopoietic stem cells.

Alemtuzumab induces lymphocyte lysis by specifically linking to the glycoprotein CD52, via complement fixation and an antibody dependent cellular cytotoxicity

Indication.

The indication of alemtuzumab is chronic lymphocytic leukaemia which has become resistant to alkylating agents and fludarabine. However, in the near future, trials currently in progress will probably change its indications and possibly its administration.

Administration

Alemtuzimab should be administered intravenously, by slow infusion, in hospital, under the strict control of a competent oncologist or haematologist, with all necessary rehabilitation resources close to the patient (at least for the first infusion).

Premedication including an analgesic drug (paracetamol), an antihistaminic drug (diphenhydramine) and corticosteroids should systematically be given before every infusion of alemtuzimab.

The same cytokine release syndrome as for rituximab is feared and requires low initial dosing (3 mg on Day 1), followed by a very progressive increase (if well tolerated), 10 mg on Day 2, 30 mg on Day 3). The recommended dosage thereafter is 30 mg/day three times per week for periods of 12 weeks.

The beneficial effect of the treatment is observed before the 12th week.

The treatment is stopped when clinical symptoms recur or if it proves to be inefficient.

Cytokine release syndrome

It is a highly feared complication. (cf. rituximab)

Tumour lysis syndrome

It appears among patients with a very important tumour mass (cf. rituximab).

Other toxicities

Major lymphocyte depletion (which is the aim of the treatment) may have some consequences. It can last for weeks. The levels of CD4 and CD8 lymphocytes may require up to one year before being fully restored.

There is therefore is an increased risk of opportunistic infections which may require general prophylactic antibiotics (trimethoprime / sulfamethoxazole) and efficient antiherpetic treatment for up to two months. If severe infections occur, alemtuzumab should not be prescribed again.

Neutropaenia and thrombocytopaenia may be observed at the beginning of the treatment (although they have only minute levels of CD 52 on their cell surface).