Immunotherapy in Acute Leukemias: Past Success Paves the Way for Future Progress

Immunotherapy as a cancer treatment modality has undergone recent widespread proliferation across all cancer types, especially amongst patients with solid tumors. However, the longest tenured immunotherapy approach to cancer is allogeneic stem cell transplantation (allo-SCT) for two hematologic malignancies: acute myeloid and acute lymphoid leukemia (AML and ALL, respectively). While allo-SCT remains a standard of care for eligible patients, recent advances/applications of monoclonal antibodies, immune checkpoint inhibitors, bispecific T-cell engagers (BiTEs), and CAR T-cell therapy are changing the treatment landscape for these acute leukemias by either direct to tumor immune targeting or through decreased toxicities that expand patient eligibility. Pre-clinical data and clinical trials have shown promising results for novel immunotherapies in acute leukemia, and multiple ongoing trials are investigating these novel approaches. While there have been promising results with these approaches, particularly in the relapsed/refractory setting, there remain challenges in optimizing the use of these therapies, such as managing cytokine release syndrome and other immune-related toxicities. Immunotherapy is a rapidly evolving field in the treatment of acute leukemia and has the potential to significantly impact the management of both AML and ALL. This review highlights the history of immunotherapy in the treatment of acute leukemias, the evolution of immunotherapy into more targeted approaches, the potential benefits and limitations of different immune targeting approaches, and ongoing research and development in the field.