Aldesleukin

Summary

Aldesleukin (Proleukin) is a recombinant form of human IL-2 approved for the treatment of metastatic renal cell carcinoma and metastatic melanoma. It promotes T-cell and NK-cell proliferation and cytotoxicity but carries a significant toxicity profile including capillary leak syndrome, requiring administration in specialized settings.

Mechanism of Action

Recombinant human interleukin-2 (IL-2) analogue that binds to IL-2 receptors on T lymphocytes and NK cells, stimulating proliferation and activation of cytotoxic T cells and natural killer cells, enhancing immune-mediated tumor destruction.

Routes of Administration

Goals & Uses

• Metastatic renal cell carcinoma treatmentOncologyHigh
• Immune reconstitution in HIVInfectious DiseaseModerate
• Combination immunotherapy potentiationOncologyModerate
• Metastatic melanoma treatmentOncologyHigh
• Regulatory T-cell expansion (low-dose)Autoimmunity / ResearchLow

Contraindications

• Organ allografts requiring immunosuppressionTransplantationHigh
• Hypersensitivity to aldesleukin or any excipientAllergyHigh
• Prior severe toxicity on previous IL-2 coursePrior Treatment HistoryHigh
• Serious infections or sepsisInfectious DiseaseHigh
• Active autoimmune diseaseAutoimmunityHigh
• Abnormal thallium stress test or pulmonary function testsCardiovascular/PulmonaryHigh

Adverse Effects

• Oliguria / renal impairmentRenalCommon
• Capillary leak syndromeVascularCommonLeakage of fluid from blood vessels into tissues
• HypotensionCardiovascularCommonLow blood pressure
• Fever and chillsConstitutionalCommon
• Neuropsychiatric effects (confusion, somnolence)NeurologicalCommon
• Thrombocytopenia and anemiaHematologicCommon

Drug Interactions

• Nephrotoxic agents (e.g., aminoglycosides, NSAIDs)High
• CorticosteroidsModerate
• Cardiotoxic agents (e.g., doxorubicin)High
• AntihypertensivesHighMay potentiate hypotensive effects in some contexts
• Interferon-alphaModerate

Population Constraints

• PregnancyReproductive SafetyRelative
• Patients with CNS metastasesDisease RelatedRelative
• Pediatric patientsAgeRelative
• Patients with hepatic impairmentOrgan FunctionRelative
• Elderly patients (≥65 years)Age RelatedRelative

Regulatory Status

• European UnionApprovedApproved: Metastatic renal cell carcinomaEMA approved; melanoma indication not universally approved across all EU member states.
• United StatesApprovedApproved: Metastatic renal cell carcinoma, Metastatic melanomaFDA approved 1992 (RCC) and 1998 (melanoma). Black Box Warning for capillary leak syndrome.
• United KingdomApprovedApproved: Metastatic renal cell carcinomaApproved by MHRA; usage has declined with advent of targeted therapies and checkpoint inhibitors.

FDA-approved since 1992 for metastatic renal cell carcinoma; approval extended to metastatic melanoma in 1998. Carries a Black Box Warning for capillary leak syndrome, impaired neutrophil function, and increased risk of serious infections. Use restricted to patients with normal cardiac and pulmonary function.

Evidence & Sources

No sources recorded yet.