Immunotherapy in adult acute lymphoblastic leukemia: current therapeutic landscape

Summary Adult acute lymphoblastic leukemia (ALL) is undergoing a major transformation, driven by the integration of monoclonal antibodies, bispecific T‑cell engagers, and chimeric antigen receptor (CAR) T‑cell therapies into treatment algorithms. This short review summarizes current evidence for the frontline management of Philadelphia chromosome (Ph)-negative and Ph-positive B‑cell precursor (BCP) ALL, the treatment of relapsed/refractory (R/R) disease, and the evolving role of allogeneic hematopoietic cell transplantation (HCT). In Ph-negative BCP-ALL, the phase 3 ECOG-ACRIN E1910 trial established blinatumomab consolidation as a new standard of care for patients who achieve measurable residual disease (MRD) negativity. For older or unfit patients, reduced-intensity or chemotherapy-free immunotherapy-based regimens have achieved high remission rates with low early mortality. In Ph-positive ALL, ponatinib has increasingly replaced imatinib as the preferred tyrosine kinase inhibitor in contemporary regimens, while chemotherapy-free ponatinib plus blinatumomab, as evaluated in GIMEMA ALL2820, has emerged as an important therapeutic benchmark. In R/R disease, blinatumomab and inotuzumab ozogamicin demonstrated superiority over conventional chemotherapy in the TOWER and INO-VATE trials, respectively, while chimeric antigen receptor (CAR) T‑cell therapies have further expanded effective treatment options. The role of HCT is increasingly guided by disease risk and depth of MRD response. Transplantation may be safely omitted in selected standard-risk patients who achieve MRD negativity, whereas high-risk subgroups, including Ph-like and TP53 -mutated ALL, may continue to benefit from HCT despite MRD negativity. Collectively, these advances signal a shift toward more effective, less toxic, and increasingly chemotherapy-sparing treatment strategies for patients with ALL.