- 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.