Abstract
Immunotherapy has transformed the treatment of acute lymphoblastic leukemia (ALL) over the past 2 decades with excellent outcomes in both adults and children particularly in the relapsed/refractory (R/R) disease setting where in general the treatment outcomes are dismal. Several immune therapies including monoclonal antibodies, bispecific T cell engagers, antibody-drug conjugates, and chimeric antigen receptor T-cells have shown excellent outcomes and safety in this setting. Based on the observed high response rates and improved survival outcomes in patients with R/R ALL, immunotherapy is now being prospectively studied in the upfront setting with an aim to reduce treatment related toxicity and death with conventional chemotherapy. In this manuscript we discuss the various clinical trials that have shown excellent outcomes in the frontline setting and discuss how best to incorporate them in newly diagnosed, treatment naïve ALL patients either as monotherapy or in combination with cytotoxic agents.