Integration of immunotherapy into the frontline treatment of acute lymphoblastic leukemia

Immunotherapy has transformed the treatment of acute lymphoblastic leukemia (ALL) over the past 2 decades, leading to excellent outcomes in adults and children. This is especially true in the setting of relapsed and refractory (R/R) disease, in which treatment outcomes formerly were dismal. Several immune therapies have shown efficacy and safety in the R/R setting, including monoclonal antibodies, bispecific antibodies, antibody-drug conjugates (ADCs), and chimeric antigen receptor (CAR) T-cell therapy. These new immunotherapy approaches have brought about a major paradigm shift in the treatment of R/R ALL, with very few long-term side effects in comparison with standard chemotherapy. These agents are now being used in patients with newly diagnosed ALL, with good response rates. This review discusses novel immunotherapeutic options, including bispecific antibodies, ADCs, and CAR T-cell-based therapies, in the upfront setting. It also discusses the incorporation of novel agents either as monotherapy or in combination with cytotoxic chemotherapy and describes our views on how best to use these agents in patients with newly diagnosed disease.