Relapsed T Cell ALL: Current Approaches and New Directions.

Patients with relapsed T cell acute lymphoblastic leukemia (T-ALL) have limited therapeutic options and a poor prognosis. Although a variety of salvage chemotherapy regimens may be used, response rates are unsatisfactory. This article summarizes current approaches and promising emerging strategies for the treatment of relapsed T-ALL. Although nelarabine is the only agent approved specifically for T-ALL, recent studies have identified a variety of genetic alterations and signaling pathways that are critical in its pathogenesis. Based on these findings, a number of small-molecule inhibitors and other targeted therapies are being studied for relapsed T-ALL, including gamma-secretase inhibitors, BCL-2 inhibitors, cyclin-dependent kinase inhibitors, and mTOR inhibitors. In addition, pre-clinical studies of chimeric antigen receptor T cells targeting CD5 and CD7 as well as the monoclonal antibody daratumumab have shown promising results for T-ALL. Relapsed T-ALL currently remains challenging to treat, but recent pre-clinical studies of targeted and immunotherapeutic agents have shown encouraging results. A number of clinical trials investigating these approaches for T-ALL are currently underway.