Alemtuzumab

Mechanism of action
• monoclonal antibody that selectively binds to CD52, highly expressed on lymphocytes (T and B cells), depleting these cells from circulation in the periphery

Indication
•Alemtuzumab is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include relapsing-remitting disease and active secondary progressive disease, in adults.

•Because of its safety profile, the use of alemtuzumab should generally be reserved for patients who have had an inadequate response to two or more drugs indicated for the treatment of MS.

Alemtuzumab is available only through restricted distribution under a Risk Evaluation and Mitigation Strategy (REMS) Program.

Contraindications
•Alemtuzumab is not recommended for use in patients with clinically isolated syndrome (CIS) because of its safety profile.

•Contraindicated in immunodeficiency conditions including HIV infection due to prolonged reductions of CD4+ lymphocyte counts

•Contra-indicated with an active infection

•Effectiveness in paediatric patients less than 17 years of age have not been established (<21, 25?)

Pre-treatment testing
•Complete any necessary immunizations at least 6 weeks prior to treatment.

•Determine whether patients have a history of varicella or have been vaccinated for varicella zoster virus (VZV). If not, test the patient for antibodies to VZV and consider vaccination for those who are antibody-negative. Postpone treatment with alemtuzumab until 6 weeks after VZV vaccination.

•Perform tuberculosis screening according to local guidelines.

•Advise patients to avoid or adequately heat foods that are potential sources of Listeria moncytogenes prior to and throughout their treatment.

•Consider delaying alemtuzumab administration in patients with active infection until the infection is fully controlled.

•JCV testing not routinely recommended

Auto-immune reactions
•Alemtuzumab causes serious, sometimes fatal, autoimmune conditions;

•immune thrombocytopenia (2%)

•anti-glomerular basement membrane (anti-GBM) disease )- 0.3%; both can occur 2-3 years after last dose

•monitor complete blood counts with differential, serum creatinine levels, and urinalysis with urine cell counts before starting treatment and then at monthly intervals until 48 months after the last dose of alemtuzumab. LFTs and TFTs at start and three (one) monthly until 48/12; autoimmune thyroid and liver dysfunction

Malignancies
•alemtuzumab may cause an increased risk of malignancies, including

•thyroid cancer,

•melanoma,

•lymphoproliferative disorders.

•arrange baseline and yearly skin exams

•use with caution in patients with pre-existing or ongoing malignancies

Increased risk of stroke
•Serious and life-threatening stroke (including ischemic and hemorrhagic stroke) has been reported within 3 days of alemtuzumab administration.

•Increased risk of stroke with Covid 19 infection is also reported

•One case of PML with alemtuzumab in 2019 (period of lymphopenia is relatively short)

Pregnancy
•Contraception during and 4/12 post treatment

•Register patients in the pregnancy exposure registry

•Antibodies, including anti-CD52 and autoantibodies, may be transferred from the mother to the fetus during pregnancy.

• Placental transfer of anti-thyroid antibodies resulting in neonatal Graves’ disease has been reported.

•Avoid breast feeding during and for 4/12 post Rx

•Washout 90 days, but undetectable

•blood levels at 30 days

•If very fertile and lucky! can plan pregnancy between annual treatments

Links
NICE guidance 2014 updated 2020