Abstract: In recent years, the application of immunotherapy has improved the prognosis of relapsed/refractory (R/R) B cell-acute lymphoblastic leukemia (B-ALL). Blinatumomab, Inotuzumab ozogamicin (InO), and chimeric antigen receptor (CAR) T-cell therapies are the three major immunotherapeutic agents approved for the treatment of R/R B-ALL. This new strategy incorporates immunotherapy into the first line of treatment to reduce the adverse effects of chemotherapy, prolong survival, and expand treatment options for elderly patients. This article discusses new approaches for incorporating immunotherapeutic agents into firstline B-ALL treatment regimens, exploring the potential value of chemotherapy-free regimens in specific patient subgroups, to provide guidance for clinical practice.