Treatment of Acute Lymphoblastic Leukemia in Adults: Applying Lessons Learned in Children

Abstract

Although pediatric acute lymphoblastic leukemia (ALL) has cure rates of over 90%, adult ALL remains a challenging disease to treat, with cure rates roughly half those seen in children. The inferior outcomes in adults can be attributed mainly to adverse genetic features, as well as the inability-particularly of older adults-to tolerate chemotherapy. Modest improvements have been seen in outcomes for adolescents and young adults; these can largely be attributed to the use of pediatric-type combination chemotherapy regimens in patients aged 50 years or younger. In patients with Philadelphia chromosome-positive ALL, once a very-high-risk group, outcomes have markedly improved as a result of the use of tyrosine kinase inhibitors in combination with chemotherapy. The persistence of minimal residual disease has emerged as the single most important prognostic factor for ALL and is increasingly being used to help make decisions regarding allogeneic hematopoietic stem cell transplantation or novel salvage therapies. Relapsed/refractory ALL has had a dismal prognosis. In recent years, novel immune-based therapies have been developed that have shown impressive results and that have the potential to improve the outcome of relapsed ALL. These include antibody-drug conjugates, the bispecific T-cell-engaging antibody blinatumomab, and chimeric antigen receptor-modified T cells.