The evolving therapeutic revolution in adult acute lymphoblastic leukemia

Abstract

The past decade has witnessed remarkable advances in deciphering the pathophysiology of acute lymphoblastic leukemia (ALL) and in developing novel targeted therapies. Basic research and genomic mapping have identified new prognostic biomarkers, targets, and ALL subtypes (e.g., Philadelphia-like ALL). The ongoing therapeutic revolution in ALL is driven by the addition to the treatment arsenal of therapies that target the ABL fusions, like the BCR::ABL1 tyrosine kinase inhibitors, as well as novel agents that target CD19 and CD22: the CD22 antibody–drug conjugate inotuzumab ozogamicin, the bispecific CD3/CD19 T-cell engager antibody blinatumomab, and CD19 chimeric antigen receptor T-cell therapies. These combinations have improved the long-term survival rates in B-cell ALL to 70%, and in Philadelphia chromosome-positive ALL to 80%–90%. The desired goals are to achieve cure rates comparable to those in pediatric ALL and to reduce or eliminate the need for prolonged intensive/maintenance chemotherapy and associated toxicities.