T-lineage
acute lymphoblastic leukemia (
T-ALL) is curable for most children and adolescent and young adult patients with contemporary frontline
chemotherapy regimens. During the past decade, improved survival rates have resulted from the optimization of frontline
chemotherapy regimens, the use of
minimal residual disease (MRD) assessment for evaluating a patient's risk for relapse, and the intensification of treatment based on the persistence of MRD. Optimization of initial
therapy is critical because relapsed
T-ALL after initial intensive
chemotherapy is incurable for most adult patients. Current
T-ALL salvage
chemotherapy regimens are minimally effective, and unlike in B-cell ALL, there are no approved antibody
therapies or
chimeric antigen receptor T-cell
therapies for relapsed disease.
Immunotherapy and small-molecule inhibitors are beginning to be tested in relapsed
T-ALL and have the potential to advance the treatment. Until effective salvage strategies are discovered, however, intensive frontline
therapy is required for cure. In this article I review the current frontline
chemotherapy regimens for adult patients with
T-ALL, summarize the novel targeted and immune
therapeutics currently in early-phase clinical trials, and outline how these
therapies are helping to define an optimal approach for
T-ALL.