alemtuzumab

**Mechanism:** Humanized IgG1 kappa monoclonal antibody that binds CD52, a GPI-anchored surface glycoprotein of unclear function expressed on mature lymphocytes (B and T), NK cells, monocytes, macrophages, and some dendritic cells. It is not expressed on hematopoietic stem cells or plasma cells. Binding leads to complement-dependent cytotoxicity (CDC), antibody-dependent cell-mediated cytotoxicity (ADCC), and apoptosis, which causes rapid and prolonged lymphocyte depletion. In MS, lymphocytes repopulate in an altered pattern. B cells recover first, and T cells recover over a longer time. This is thought to produce a "reset" of the immune repertoire with relatively more regulatory cells.

**Indications:** - *B-cell CLL* (Campath, 30 mg IV or SC three times weekly): especially fludarabine-refractory disease and CLL with 17p deletion/TP53 mutation, which responds poorly to chemoimmunotherapy. - *Relapsing-remitting MS* (Lemtrada, 12 mg/day IV for 5 days, then 3 days a year later): highly active disease, reserved for patients who have had an inadequate response to two or more other MS drugs. - *Off-label or other uses:* T-cell prolymphocytic leukemia, conditioning regimens before hematopoietic stem cell transplant, GVHD prophylaxis/treatment, and induction in solid organ transplant (e.g., kidney).

**Adverse effects (high-yield):** - *Infusion reactions:* cytokine release causes fever, rigors, rash, hypotension, and dyspnea. Premedicate with corticosteroids, antihistamines, and antipyretics. - *Immunosuppression:* opportunistic infections (CMV reactivation, PJP, herpes viruses, Listeria, fungal infections, and rarely PML). Prophylaxis (acyclovir, PJP prophylaxis) and CMV monitoring are standard in CLL. For MS, screen for TB, HBV, HCV, HIV, and HPV, and counsel on avoiding Listeria-containing foods. - *Cytopenias:* neutropenia, anemia, thrombocytopenia. - *Secondary autoimmunity (especially in MS, because of the immune reconstitution):* autoimmune thyroid disease (Graves disease more than hypothyroidism), immune thrombocytopenia (ITP), autoimmune hemolytic anemia, and anti-glomerular basement membrane disease (Goodpasture-type). Monitor CBC, creatinine, urinalysis, and TSH monthly for at least 48 months after the last dose. - *Other boxed warnings (Lemtrada):* stroke (including cervicocephalic arterial dissection, usually within days of infusion), malignancy (thyroid cancer, melanoma, lymphoproliferative disorders), and REMS-restricted access. Campath has boxed warnings for cytopenias, infusion reactions, and infections. - *Blood products:* irradiate cellular blood products to prevent transfusion-associated GVHD. - *Live vaccines:* contraindicated.

**Board pearls:** - Target to remember: Alemtuzumab → CD52. Compare rituximab → CD20, and brentuximab → CD30. - Name stem: "-mab" means monoclonal antibody, and "-zu-" means humanized. - Mnemonic: "Alemtuzumab = All lymphocytes (CD52), CLL and MS." - Question stem pattern: a patient with MS who gets alemtuzumab develops hematuria, hemoptysis, or renal failure. Think anti-GBM disease. A patient with weight loss, palpitations, and exophthalmos after alemtuzumab suggests Graves disease. - Comparison with other MS drugs: natalizumab (α4-integrin) carries a PML risk. Ocrelizumab and ofatumumab (anti-CD20) carry infection and hypogammaglobulinemia risk. Fingolimod (S1P modulator) carries bradycardia and macular edema risk.