Ph− ALL: immunotherapy in upfront treatment

Antibody-based and cell-based novel immunotherapies, such as bispecific T-cell engagers (BiTE), antibody-drug conjugates, or chimeric antigen receptor (CAR) T cells are currently standard treatment options for patients with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL). To date, CD20-targeting monoclonal antibodies and the CD19-targeting BiTE's blinatumomab have been established elements of frontline therapy, either in patients with CD20+ ALL or in patients with measurable disease (MRD) following conventional chemotherapy. Recently, blinatumomab has also demonstrated a survival benefit in patients with MRD-negative ALL. Based on the observed high response rates and improved survival outcomes in patients with R/R ALL, antibody-based immunotherapies are being prospectively studied in the upfront setting, particularly in older adult patients, where even age-adapted conventional chemotherapies are still associated with significant rates of early death, treatment-related toxicity, and poor prognosis. In these approaches, conventional chemotherapy has been replaced or reduced and supplemented by immunotherapeutic agents, resulting in promising outcomes that form the basis for evaluating and defining new treatment standards.