Alemtuzumab

Usage

Alemtuzumab is prescribed for the treatment of:

• B-cell chronic lymphocytic leukemia (B-CLL)
• Relapsing forms of multiple sclerosis (MS), including relapsing-remitting disease and active secondary progressive disease. It is generally reserved for patients who have had an inadequate response to two or more other MS drugs.

Pharmacological Classification: Alemtuzumab is a monoclonal antibody, classified as a disease-modifying therapy (DMT) in MS and a targeted therapy in B-CLL. It also functions as an immunosuppressant.

Mechanism of Action: Alemtuzumab targets the CD52 protein, found on the surface of B and T lymphocytes (types of white blood cells). By binding to CD52, it triggers the destruction of these cells, thereby suppressing immune responses. In MS, this helps to reduce the inflammatory attacks that damage the nervous system. In B-CLL, it targets the malignant B-cells.

Alternate Names

Alemtuzumab is marketed under the brand names Campath (for B-CLL) and Lemtrada (for MS). There are no widely used alternate names.

How It Works

Pharmacodynamics: Alemtuzumab causes profound, prolonged depletion of circulating lymphocytes, primarily B and T cells, which leads to immunomodulation. After treatment, lymphocyte repopulation occurs, with a shift toward a higher proportion of naive T and B cells.

Pharmacokinetics: Administered intravenously, alemtuzumab exhibits concentration-dependent clearance. Alemtuzumab is a monoclonal IgG antibody. It is absorbed slowly, and distributed primarily within the vascular and extravascular fluids. Metabolism follows pathways similar to endogenous IgG, occurring primarily via proteolytic catabolism throughout the body. Alemtuzumab is cleared relatively quickly from circulation after each course. The drug is cleared faster when given for B-CLL due to the presence of higher levels of target cells.

Mode of Action: Alemtuzumab binds to the CD52 antigen on lymphocytes. This binding initiates antibody-dependent cellular cytotoxicity and complement-mediated lysis, leading to the depletion of lymphocytes.

Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: The primary mechanism is receptor binding (CD52). Alemtuzumab does not directly inhibit enzymes or modulate neurotransmitters.

Elimination Pathways: Elimination occurs primarily through proteolytic catabolism throughout the body, similar to endogenous IgG. Renal excretion plays a minor role.

Dosage

Standard Dosage

Adults:

• Multiple Sclerosis (Lemtrada):

  • First Treatment Course: 12 mg/day IV over 4 hours for 5 consecutive days (total dose 60 mg)
  • Second Treatment Course: 12 mg/day IV over 4 hours for 3 consecutive days (total dose 36 mg) administered 12 months after the first course.

• Chronic Lymphocytic Leukemia (Campath):

  • 30 mg IV (or subcutaneously) three times a week (e.g., Monday, Wednesday, Friday) over 2 hours for up to 12 weeks. Dose escalation is required:
    • Start with 3 mg IV daily until infusion reactions are Grade 2 or less.
    • Increase to 10 mg IV daily until reactions are Grade 2 or less.
    • Then, increase to the 30 mg dose.
    • Re-escalation is required if the dose is interrupted for 7 days or more.

Children: Not recommended. Safety and efficacy have not been established in children.

Special Cases:

• Elderly Patients: No specific dose adjustment recommended.
• Patients with Renal Impairment: No dose adjustment recommended.
• Patients with Hepatic Dysfunction: No dose adjustment recommended.
• Patients with Comorbid Conditions: Careful monitoring required, especially with autoimmune conditions or pre-existing infections.

Clinical Use Cases

Alemtuzumab is not indicated for intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations.

Dosage Adjustments

Dose modifications may be required for severe adverse reactions. If treatment is interrupted for seven or more days, re-escalation of the dose is necessary.

Side Effects

Common Side Effects:

• Infusion reactions (headache, rash, fever, nausea, fatigue, itching, flushing)
• Upper respiratory tract infections
• Urinary tract infections
• Sinusitis
• Lymphopenia (low lymphocyte counts)
• Thyroid dysfunction (hypothyroidism or hyperthyroidism)

Rare but Serious Side Effects:

• Autoimmune conditions (e.g., idiopathic thrombocytopenic purpura (ITP), autoimmune thyroid disease, Goodpasture’s syndrome, acquired hemophilia A)
• Progressive multifocal leukoencephalopathy (PML)
• Serious infections (due to immunosuppression)

Long-Term Effects:

• Risk of secondary autoimmune diseases can persist for years after treatment.
• Long-term monitoring for thyroid abnormalities is essential.

Adverse Drug Reactions (ADR):

• Anaphylaxis (rare)
• Severe infusion reactions

Contraindications

• HIV infection
• Active serious infections
• Hypersensitivity to alemtuzumab or any of its components

Drug Interactions

Limited data exists on drug-drug interactions. However, due to its mechanism of action, caution should be used with other immunosuppressants. Live vaccines should be avoided during and after treatment.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: Contraindicated. Alemtuzumab can cause fetal harm. Women of childbearing potential should use effective contraception during and for four months after treatment.
• Breastfeeding: Contraindicated. It is unknown if alemtuzumab passes into breast milk. Breastfeeding should be avoided during and for three months after treatment.

Drug Profile Summary

• Mechanism of Action: Binds to CD52 on lymphocytes, causing their depletion.
• Side Effects: Infusion reactions, infections, autoimmune conditions, thyroid disorders.
• Contraindications: HIV, active serious infections, hypersensitivity.
• Drug Interactions: Limited data, caution with immunosuppressants; avoid live vaccines.
• Pregnancy & Breastfeeding: Contraindicated.
• Dosage: MS: 12 mg/day x 5 days for the first course, 12 mg/day x 3 days for the second course (12 months later). B-CLL: 30 mg IV three times weekly for up to 12 weeks (dose escalation required).
• Monitoring Parameters: Complete blood count, thyroid function tests, urine protein, signs of infection, autoimmune conditions.

Popular Combinations

For MS, alemtuzumab is typically used as a single agent. In B-CLL, alemtuzumab is used as single agent, but can be combined with other chemotherapy drugs depending on the regimen.

Precautions

• Monitor for infections and autoimmune reactions.
• Pre-screening for tuberculosis, hepatitis B and C is recommended.
• Patients should avoid live vaccinations during and after treatment.
• Thorough patient counseling is essential to ensure understanding of risks and benefits.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Alemtuzumab?

A: For MS (Lemtrada): 12 mg/day IV for 5 days for the first course, followed by 12 mg/day IV for 3 days 12 months later. For B-CLL (Campath): 30 mg IV three times a week, after dose escalation.

Q2: What are the most serious side effects of Alemtuzumab?

A: Autoimmune conditions (ITP, thyroid disease, Goodpasture’s syndrome, acquired hemophilia A), PML, and serious infections.

Q3: Can Alemtuzumab be used during pregnancy or breastfeeding?

A: No, alemtuzumab is contraindicated in both pregnancy and breastfeeding.

Q4: How does Alemtuzumab work in multiple sclerosis?

A: It depletes lymphocytes, reducing the inflammatory attacks on the nervous system.

Q5: How does Alemtuzumab work in B-cell chronic lymphocytic leukemia?

A: It targets and destroys malignant B-cells.

Q6: What are the common infusion reactions associated with Alemtuzumab?

A: Headache, rash, fever, nausea, fatigue, itching, and flushing.

Q7: What monitoring is required for patients receiving Alemtuzumab?

A: Regular blood counts, thyroid function tests, urine protein monitoring, and vigilance for signs of infection and autoimmune disease.

Q8: Are there any contraindications to Alemtuzumab use?

A: Yes, HIV infection, active serious infection, and hypersensitivity to the drug are contraindications.

Q9: Can patients receive vaccinations while on Alemtuzumab?

A: Live vaccines should be avoided during and after treatment. Consult with the treating physician regarding other vaccines.

Q10: What is the duration of treatment with Alemtuzumab for MS?

A: Two initial treatment courses, with additional courses possible if needed, spaced at least 12 months apart.