Alemtuzumab — Drug Monograph

Brand names: Campath, Lemtrada, MabCampath

Drug class: Monoclonal Antibody

Mechanism of Action

Humanized anti-CD52 monoclonal antibody (IgG1κ). CD52 is highly expressed on the surface of B and T lymphocytes, NK cells, monocytes, and macrophages. Binding triggers antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), producing profound and prolonged depletion of circulating lymphocytes. Its mechanism is p53-independent, so it retains activity in TP53-mutated / 17p-deleted disease.

FDA Indications

• B-cell chronic lymphocytic leukemia (B-CLL) as a single agent (Campath). Note: withdrawn from general oncology marketing in 2012 and made available for CLL only through a restricted patient-support program after the drug was relaunched at a higher dose as Lemtrada for multiple sclerosis.
• Relapsing forms of multiple sclerosis (Lemtrada) — reserved for patients with inadequate response to ≥2 prior therapies (non-oncology indication)

Common Side Effects

• Infusion reactions (fever, chills, rigors, hypotension, rash)
• Profound lymphopenia and immunosuppression
• Neutropenia, anemia, thrombocytopenia
• CMV and other opportunistic infections
• Nausea
• Fatigue

Clinical Pearl

Alemtuzumab produces one of the most profound and durable lymphodepletions of any oncology antibody — CD4 counts can stay suppressed for more than a year, so PJP and antiviral (herpes/CMV) prophylaxis is mandatory. Because its cytotoxicity is p53-independent it retains activity in TP53-mutated / 17p-deleted CLL, but it has been largely superseded by BTK inhibitors and venetoclax-based regimens. It remains clinically important for T-PLL and, as Lemtrada, for multiple sclerosis.

Related Therapies & Mechanisms

• Obinutuzumab (Gazyva) — Monoclonal Antibody · Lymphoma
• Ofatumumab (Arzerra) — Monoclonal Antibody · Leukemia
• Rituximab (Rituxan) — Monoclonal Antibody · Lymphoma
• Blinatumomab (Blincyto) — Monoclonal Antibody · Leukemia