Acute Lymphoblastic Leukemia in the Older Adult

Acute lymphoblastic leukemia (ALL) in older adults presents a real challenge as a result of adverse disease biology and comorbidities that preclude delivering curative regimens. Conventional chemotherapy approaches have generally yielded unsatisfactory results in older patients with ALL as a result of excessive induction mortality, chemotherapy resistance of the leukemia, and the need to omit or dose reduce key drugs during the course of therapy because of adverse effects. Philadelphia chromosome-positive ALL represents about a quarter of newly diagnosed older adults, and the striking single-agent activity and excellent safety profile of tyrosine kinase inhibitors has allowed incorporation of these agents into therapy, significantly improving the outcome of older adults with Philadelphia chromosome-positive ALL. Allogeneic hematopoietic cell transplantation using reduced-intensity conditioning is a potentially curative approach in the older adult with ALL, and ironically, it may be better tolerated than intensive combination chemotherapy in a subset of older patients with ALL. Immunotherapies such as chimeric antigen receptor-modified T-cells, the bispecific T-cell-engaging antibody targeting CD19 (blinatumomab), and the antibody-drug conjugate targeting CD22 (inotuzumab) have shown safety and exceptional activity even in advanced ALL, and the efficacy of these agents has been observed irrespective of patient age. Several promising studies tailored specifically toward older adults with ALL are ongoing, with the majority of them incorporating novel immunotherapies, targeted therapies, or third-generation tyrosine kinase inhibitors into the front-line treatment regimen.