Nelarabine

Nelarabine is an antineoplastic agent that is typically used to treat acute T-cell lymphoblastic leukemia, particularly T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL), in both adult and pediatric patients whose disease has not responded to or has relapsed following at least two chemotherapy regimens. T-cell acute lymphoblastic leukemia and lymphoma are relatively rare T-cells malignancy, with only 20 to 25% of patients diagnosed with acute lymphoblastic leukemia and 1.7% of patients diagnosed with non-Hodgkin's lymphoma having this T-cells variation of the disease. Due to the rarity of these T-cell malignancies, nelarabine was first granted orphan drug status and a fast-track designation by the FDA to address the unmet therapeutic needs of these cancers. Nelarabine is a purine nucleoside analog converted to its corresponding arabinosylguanine nucleotide triphosphate (araGTP), resulting in the inhibition of DNA synthesis and cytotoxicity. Nelarabine preferentially accumulates in T-cells since T-cells have a higher expression of enzymes that convert nelarabine to the active purine analog form, making them effective against T-cells malignancies. Results from 2 phase 2 studies on adult and pediatric T-ALL/T-LBL indicated that nelarabine can yield a 13% complete response (CR) rate in pediatric patients and 18% in adult patients, albeit with serious hematological and neurological adverse events. Nelarabine was first granted accelerated approval by the FDA on October 28, 2005, and was manufactured under the trademark name ARRANON by GlaxoSmithKline. Subsequently, nelarabine was also approved by both Health Canada and European Medicines Agency in 2007 under the trademark name ATRIANCE.