Nelarabine — Drug Monograph

Brand names: Arranon

Drug class: Antimetabolite

Mechanism of Action

Nelarabine is a prodrug of the deoxyguanosine analogue guanine arabinoside (ara-G). It is rapidly demethylated by adenosine deaminase to ara-G, which is then phosphorylated by deoxyguanosine kinase and deoxycytidine kinase to the active 5'-triphosphate form, ara-GTP. Accumulation of ara-GTP in leukemic blasts leads to its incorporation into DNA, resulting in inhibition of DNA synthesis and induction of apoptosis. Because T-cells have higher deoxyguanosine kinase activity and lower nucleotidase activity than B-cells, nelarabine shows selective cytotoxicity toward T-lymphoblastic malignancies.

FDA Indications

• Treatment of patients with T-cell acute lymphoblastic leukemia (T-ALL) whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens
• Treatment of patients with T-cell lymphoblastic lymphoma (T-LBL) whose disease has not responded to or has relapsed following treatment with at least two chemotherapy regimens

Common Side Effects

• Anemia
• Thrombocytopenia
• Neutropenia
• Nausea
• Vomiting
• Diarrhea
• Constipation
• Fatigue
• Somnolence
• Dizziness

Clinical Pearl

The dose-limiting toxicity for nelarabine is its profound neurotoxicity, which can manifest as anything from mild somnolence to irreversible paraplegia. Patients must be monitored extremely closely for any new sensory or motor changes, and the drug should be discontinued at the first sign of Grade 2 or higher neurologic symptoms. Unlike many other antimetabolites, nelarabine has a specific predilection for T-cell lineages, making it a niche but vital agent for refractory T-ALL. Since it is a…

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