Immunotherapy in Acute Myeloid Leukemia Lacks Breakthroughs, Researchers Argue

Current studies on oncology, specifically acute myeloid leukemia, have revealed a significant disparity between the effectiveness of immunotherapy in lymphoid malignancies and its lackluster performance in acute myeloid leukemia. Despite dramatic improvements in outcomes for lymphoid malignancies, such as B cell cancers, AML has not experienced a comparable breakthrough. Researchers at University Hospital LMU Munich pointed to the biological and immunologic complexity of AML, which hinders the development of targeted therapies.

Key Takeaways:

• Immunotherapy has shown promising results in lymphoid malignancies, particularly in B cell cancers, with CD19-directed CAR T cells and T-cell engagers achieving high remission rates.
• In contrast, acute myeloid leukemia has not seen a comparable breakthrough, with only antibody-drug conjugates, such as gemtuzumab ozogamicin, reaching regulatory approval.
• The lack of leukemia-specific antigens in AML, shared targets with normal hematopoietic progenitors, and immunosuppressive mechanisms make it challenging to develop effective immunotherapies.
• Researchers have highlighted the importance of integrating immune contexture of the bone marrow environment and establishing rational combinatorial approaches to overcome AML's immunosuppressive properties.
• Marion Subklewe, Sergio Rutella, and Antonio Curti, along with other researchers, are working towards developing personalized immunotherapies for AML patients.
• The current immunotherapy landscape in AML is limited, and researchers aim to redefine knowledge gaps by synthesizing recent clinical data and mechanistic insights.

Statistics:

• Only antibody-drug conjugates, such as gemtuzumab ozogamicin, have reached regulatory approval for newly diagnosed CD33-positive AML.
• Current immunotherapy platforms under investigation in AML include antibody-based approaches (e.g., antibody-drug conjugates), T-cell redirecting therapies (e.g., CAR T cells and T-cell engagers), and personalized combinatorial strategies.
• The bone marrow microenvironment plays a crucial role in AML's immunosuppressive mechanisms, with tumor-intrinsic and microenvironmental mechanisms affecting T-cell persistence and function.
• According to recent clinical data, CAR and T-cell engager trials have shown promise, but more research is needed to overcome AML's immunosuppressive properties.
• The researchers aim to provide a translational framework for how immunotherapy might still reshape AML care through integration of immune contexture of the bone marrow environment aiming for rational combinatorial approaches.

Sources:

• "The immunotherapy landscape in AML: Defining knowledge gaps toward rational combinatorial strategies." Seminars In Hematology, 2025.
• University Hospital LMU Munich, Department of Medicine III.
• W B Saunders Co-elsevier Inc, 1600 John F Kennedy Boulevard, Ste 1800, Philadelphia, PA 19103-2899, USA.