Management of Adult Acute Lymphoblastic Leukemia

Importance: Research in acute lymphoblastic leukemia (ALL) is translating into rapid changes in therapy and outcomes. Historically, adult ALL was treated with intensive chemotherapy extending over 2.5 to 3 years. This established tradition, accepted because of the high cure rates in childhood ALL, has been challenged by the development of highly active targeted therapies. Observation: Treatment modalities, combined with less and shorter chemotherapy durations, have produced better results than chemotherapy. The novel therapies include using the more potent BCR::ABL1 tyrosine kinase inhibitors (eg, ponatinib, dasatinib) with the bispecific CD3-CD19 T-cell engager antibody blinatumomab in Philadelphia chromosome-positive ALL and combining blinatumomab and/or inotuzumab (CD22 antibody drug conjugate) with standard chemotherapy in B-cell ALL. These have been associated with improved 4-year survival rates of 85% to 90% in Philadelphia chromosome-positive ALL and 80% to 85% in B-cell ALL. Conclusions and Relevance: The management of ALL is changing rapidly. Investigators have evaluated frontline and later-line regimens with combinations of tyrosine kinase inhibitors and immunotherapies with less or no chemotherapy. Future research will evaluate CD19, CD20, and CD22 multitargeting antibodies and chimeric antigen receptor T-cell therapies, new antibody formulations, and less intensive/shorter regimens.