Where do immunotherapies stand in management of acute leukemia in adults?

Immunotherapies have significantly transformed the treatment landscape of acute leukemia in adults, most notably in B-cell acute lymphoblastic leukemia (B-ALL). Blinatumomab and inotuzumab ozogamicin have become established treatments, enhancing remission rates, measurable residual disease clearance, and overall survival in relapsed/refractory disease, and these agents, are now increasingly incorporated into frontline therapy. Additionally, autologous CD19 chimeric antigen receptor (CAR) T-cell therapy has dramatically improved salvage treatment outcomes, demonstrating exceptional remission rates and durable responses even in heavily pretreated patients. Enhanced understanding of mechanisms underlying disease resistance and relapse is guiding the development of optimized combination and sequential therapeutic approaches. In acute myeloid leukemia (AML), gemtuzumab ozogamicin has shown significant clinical benefits, particularly in molecularly defined subsets. Ongoing research focuses on novel antibody-drug conjugates, immune cell engagers, and advanced cellular therapies, facing challenges primarily in selecting appropriate targets and overcoming the immunosuppressive tumor microenvironment. For T-cell acute lymphoblastic leukemia (T-ALL), therapeutic innovation is confronted with unique challenges due to overlapping antigen expression between malignant, normal, and CAR T-cells. Promising early clinical and preclinical studies are currently evaluating anti-CD38 antibodies and CAR T-cells mostly directed against CD5 and CD7. This review highlights how immunotherapy has reshaped treatment paradigms across acute leukemias, underscoring successful experiences in B-ALL. These insights emphasize the need for continued innovation to overcome existing hurdles in AML and T-ALL, ultimately aiming to enhance patient outcomes and quality of life.