Introduction
Campath (alemtuzumab) is a monoclonal antibody medication that targets the CD52 antigen present on lymphocytes and other immune cells. Originally developed at the University of Cambridge, it has undergone significant evolution in its clinical applications from initially being used in hematologic malignancies to its current primary use in multiple sclerosis. Campath represents a unique approach to immunomodulation through targeted lymphocyte depletion.
Mechanism of Action
Alemtuzumab is a recombinant DNA-derived humanized monoclonal antibody directed against the 21-28 kD cell surface glycoprotein CD52. CD52 is expressed on the surface of B and T lymphocytes, monocytes, macrophages, and natural killer cells. Upon binding to CD52, alemtuzumab mediates antibody-dependent cellular cytolysis and complement-mediated lysis of these cells. The resulting lymphopenia is followed by a distinctive pattern of T-cell repopulation that alters the balance of the immune system, making it particularly useful in autoimmune conditions like multiple sclerosis.
Indications
- Treatment of relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease
- Previously was indicated for the treatment of B-cell chronic lymphocytic leukemia (this indication has been discontinued in many markets)
Dosage and Administration
Multiple sclerosis dosing regimen:- Initial treatment course: 12 mg/day administered by intravenous infusion for 5 consecutive days (total 60 mg)
- Subsequent treatment course: 12 mg/day administered by intravenous infusion for 3 consecutive days (total 36 mg) 12 months after the initial treatment
- Premedication with corticosteroids (e.g., methylprednisolone 1,000 mg/day) is recommended immediately prior to Campath infusion to mitigate infusion reactions
- Administer as an intravenous infusion over approximately 4 hours
- Subsequent courses are administered at least 12 months apart after initial treatment
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: No dosage adjustment necessary
- Elderly: Use with caution due to increased risk of infections
Pharmacokinetics
Absorption: Administered intravenously, resulting in complete bioavailability Distribution: Volume of distribution is approximately 0.15 L/kg. Binds to CD52-positive lymphocytes throughout the body Metabolism: Undergoes proteolytic degradation Elimination: Half-life is approximately 2 weeks. Clearance decreases with repeated administration due to depletion of CD52-positive cells Special populations: No significant differences based on age, gender, or raceContraindications
- Human immunodeficiency virus (HIV) infection
- History of hypersensitivity to alemtuzumab or any component of the formulation
- Active infection (until resolved)
- Patients with known bleeding disorders or on anticoagulant therapy (due to increased risk of hemorrhage)
Warnings and Precautions
Boxed Warning: Campath carries serious risks including:- Autoimmune disorders (thyroid disorders, immune thrombocytopenia, anti-glomerular basement membrane disease)
- Serious and sometimes fatal infusion reactions
- Increased risk of malignancies including thyroid cancer, melanoma, and lymphoproliferative disorders
- Serious infections including Listeria meningitis, tuberculosis, and herpes viral infections
- Increased risk of stroke and arterial dissection
- Requires mandatory Risk Evaluation and Mitigation Strategy (REMS) program
- Monitor for symptoms of autoimmune disorders for 48 months after last dose
- Prophylaxis for herpes viral infections recommended
- Vaccination with live vaccines not recommended during treatment
Drug Interactions
- Concomitant use with other immunosuppressive therapies may increase risk of infections
- Anticoagulants and antiplatelet agents may increase risk of bleeding
- Live vaccines: Avoid administration during treatment and after recent Campath therapy
- Drugs that affect heart rate or blood pressure may potentiate infusion-related cardiovascular effects
Adverse Effects
Most common (>10%):- Infusion reactions (fever, headache, rash, nausea, urticaria, pruritus)
- Infections (upper respiratory tract, urinary tract, herpes viral)
- Thyroid disorders
- Lymphopenia
- Autoimmune thyroid disorders (23% of patients)
- Immune thrombocytopenia (2%)
- Nephropathies (including anti-GBM disease)
- Infections (including opportunistic infections)
- Malignancies
- Stroke and arterial dissection
- Hemophagocytic lymphohistiocytosis
Monitoring Parameters
Prior to initiation:- Complete blood count with differential
- Serum creatinine
- Urinalysis with microscopy
- Thyroid function tests (TSH)
- Tuberculosis screening
- HIV screening
- Hepatitis B and C screening
- Baseline skin examination
- Monthly complete blood count with differential for 48 months after last dose
- Serum creatinine and urinalysis with microscopy monthly for 48 months after last dose
- Thyroid function tests every 3 months
- Regular monitoring for signs and symptoms of autoimmune disorders, infections, and malignancies
- Blood pressure and pulse during infusion
- Continue regular monitoring for autoimmune disorders for at least 4 years after last dose
- Annual skin examinations
Patient Education
- Understand the serious risks associated with Campath therapy, including autoimmune disorders and infections
- Report immediately any signs of infection, unusual bleeding or bruising, thyroid symptoms, or neurological changes
- Carry the patient safety card provided with the medication
- Use effective contraception during treatment and for 4 months after last dose
- Understand the need for regular monitoring and laboratory tests
- Recognize symptoms of infusion reactions and report them promptly
- Avoid live vaccines during treatment
- Practice infection prevention measures including safe food handling to prevent Listeria infection
References
1. FDA prescribing information: Campath (alemtuzumab) 2. Cohen JA, et al. Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1819-1828. 3. Coles AJ, et al. Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial. Lancet. 2012;380(9856):1829-1839. 4. Cuker A, et al. Immune thrombocytopenia in alemtuzumab-treated MS patients: incidence, detection, and management. Neurology. 2020;94(16):e1752-e1762. 5. Tuohy O, et al. Alemtuzumab treatment of multiple sclerosis: long-term safety and efficacy. JAMA Neurol. 2015;72(2):164-174. 6. ClinicalTrials.gov: CARE-MS I and II studies 7. EMA assessment report: Lemtrada (alemtuzumab)