Progress and Innovations in the Management of Adult Acute Lymphoblastic Leukemia

Abstract

Importance: Remarkable progress has occurred in understanding the pathophysiology and in developing improved personalized therapies in adult acute lymphoblastic leukemia (ALL).

Observations: We searched MEDLINE (1990-2018), the American Society of Clinical Oncology, and American Society of Hematology websites (2010-2018). We used the search terms "acute lymphoblastic or lymphocytic leukemia" or "ALL." We largely selected publications in the past 5 years but did not exclude commonly referenced and highly regarded older publications. Target therapies toward specific transcripts (eg, BCR-ABL1 tyrosine kinase oncoprotein by tyrosine kinase inhibitors) and specific leukemic cell surface antigens (eg, CD20, CD22, and CD19 monoclonal antibodies) are major breakthroughs. Current treatments produce long-term survival in 50% of patients with precursor B-cell ALL including 50% to 70% with Philadelphia chromosome (Ph)-positive ALL, 50% to 60% with T-cell ALL, and 80% with mature B-cell ALL. Next-generation sequencing and genomic profiling in ALL have identified new prognostic markers, targets, and ALL subtypes (eg, Ph-like ALL). Monoclonal antibodies, bispecific antibody constructs, and chimeric antigen receptor T cellular therapies developed in the past 5 to 7 years have revolutionized the treatment of ALL and resulted in US Food and Drug Administration approvals of blinatumomab in 2014, as well as inotuzumab and tisagenlecleucel in 2017 as ALL salvage strategies. Their use in combined modalities as salvage and frontline therapies is currently under investigation.

Conclusions and relevance: Therapies targeting specific transcripts or leukemic cell surface antigens are major breakthroughs in the treatment of adults with ALL. The incorporation of new monoclonal antibodies and other targeted approaches into frontline regimens is showing promising results. If confirmed, such strategies may increase the cure rates in adults to levels achieved in pediatric ALL and reduce the need for intensive and prolonged chemotherapy.