Alemtuzumab

• Class: Monoclonal antibody (mAb) – anti-CD52.
• Type: Humanized IgG1 antibody.

Mechanism of Action

• Binds to CD52, a glycoprotein expressed on:
  • B and T lymphocytes
  • NK cells
  • Monocytes and some macrophages
• Induces cell death via:
  • Complement-dependent cytotoxicity (CDC)
  • Antibody-dependent cellular cytotoxicity (ADCC)
  • Direct apoptosis in some lymphocytes

Clinical Uses

• Chronic lymphocytic leukemia (CLL) – relapsed/refractory.
• T-cell prolymphocytic leukemia (T-PLL).
• Multiple sclerosis (MS) – high-efficacy therapy in relapsing forms (Lemtrada®).

Dosing

• CLL (IV): 30 mg 3×/week for up to 12 weeks (dose-escalation often used to reduce infusion reactions).
• MS (IV): 12 mg/day for 5 consecutive days (Year 1), repeated for 3 days in Year 2.
• Requires premedication with corticosteroids, antipyretics, and antihistamines to reduce infusion reactions.

Toxicities

• Infusion-related reactions – fever, chills, hypotension, rash (very common).
• Severe immunosuppression → risk of opportunistic infections: CMV, herpes, fungal, bacterial.
• Cytopenias (lymphopenia, neutropenia, anemia).
• Autoimmune disorders: thyroiditis, ITP, autoimmune cytopenias.
• Rare: tumor lysis syndrome in high tumor burden.

Monitoring

• CBC with differential frequently (weekly during infusion period).
• CMV PCR and prophylaxis/monitoring for opportunistic infections.
• Infection prophylaxis (e.g., antivirals, PCP prophylaxis).
• Vital signs during infusion.
• Autoimmune labs during and after therapy.

In summary:

Alemtuzumab is an anti-CD52 monoclonal antibody used in CLL, T-PLL, and MS. Its hallmark is profound lymphocyte depletion, requiring intensive monitoring for infusion reactions and opportunistic infections, along with autoimmune complications.