A Review of nelarabine in the Treatment of T-cell Lymphoblastic Leukemia/Lymphoma

Patients with relapsed/refractory T-cell acute lymphocytic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) have a dismal prognosis. Prior to the development of novel purine analogs, salvage chemotherapy was of limited efficacy. Nelarabine, and more recently, clofarabine and forodesine have demonstrated significant anti-tumor activity in relapsed/refractory T-ALL and T-LBL. As a single agent, nelarabine induces response rates in between 33% to 50% of adult or pediatric patients with T-ALL/T-LBL, respectively. On the other hand, limited activity was observed in mature T-cell neoplasms. Significant neurotoxicity has been the major obstacle for the further clinical development of nelarabine. Alternative dose-schedules for administration have been evaluated with some degree of success. Ongoing clinical studies are integrating nelarabine in the front-line chemotherapy regimens for patients with T-ALL/T-LBL in pediatric and young adult patients. The current work summarizes the pre-clinical and clinical evaluation of nelarabine, a chemotherapy agent whose development demonstrates that industry, government agencies, and academia can effectively collaborate together to improve the patient outcomes with highly resistant/refractory rare hematological malignancies.