By Ivan Diaz-Padilla, Senior Vice President and Global Head, Oncology Therapeutic Area Unit, R&D at Ipsen
Acute myeloid leukemia (AML) remains a challenging blood cancer to treat
AML is a complex and highly heterogeneous cancer of white blood cells, where clinical outcomes remain uncertain despite advances in classification and treatment.1,2 Many people still relapse after achieving remission or fail to achieve long-term disease control, particularly those who are older or considered unfit for intensive chemotherapy.2,3
As scientific understanding grows, a complicated relationship between AML and the immune system is emerging. With an urgent need for novel treatment approaches, researchers are asking the question: could engaging the body’s immune system be the key to effective anti-leukemic activity?
The challenge with existing immune-based therapeutic approaches
Beyond allogeneic stem cell transplantation, where donor immune cells can help recognize and control residual AML, other immune-based treatments have struggled to deliver consistent or durable benefits.2,4,5 Immune checkpoint inhibitors, which work by blocking inhibitory pathways that limit immune activity, have shown insufficient activity as monotherapy in AML, although combination strategies are still being evaluated.6-8
These outcomes have prompted further investigation into how AML evades immune control and whether new ways of modulating the immune response could offer a therapeutic approach.5
How AML shapes and evades the immune system
Growing evidence suggests that interactions between AML and the immune system are closely linked to disease biology. Rapidly proliferating, immature AML cells, known as blasts, are thought to disrupt the normal development and function of immune cells.2 More broadly, AML cells can avoid immune detection through several mechanisms, including altering how they present antigens and releasing signals that suppress immune activity.2,9
At the same time, these cells appear to be capable of reshaping their surrounding environment in ways that weaken the immune response. This makes it harder for the immune system to recognize and eliminate residual disease, allowing cancer cells to survive treatment and eventually re-emerge, contributing to disease relapse.1,9
For people who are unable to tolerate intensive chemotherapy, the ability of AML to evade immune control may be an important area to explore further. There is growing evidence that treatment responses in these patients are typically shorter and less durable. This may therefore represent an important area of investigation for improving longer-term disease control.1,3,10
New approaches targeting the immune system in AML
These insights are now shaping the development of new treatment approaches designed to harness the immune system more effectively.
Emerging areas of investigation include:6
Activating innate and innate-like immune responses – such as antibody-based therapies and cellular approaches designed to recruit or activate immune cells
- Targeting immune regulatory pathways – building on existing approaches like checkpoint inhibitors, as well as newer strategies that aim to modulate how immune responses are controlled
- Reducing immune suppression within the bone marrow microenvironment – including approaches such as CD47-targeting therapies that may help remove barriers to immune activity
Together, these approaches reflect the breadth of ongoing research in AML. Investigational approaches may offer new possibilities for people who are unable to tolerate intensive treatment but may still benefit from immune-based strategies.
Ipsen’s approach to this challenge
One approach being explored focuses on selectively activating specific subsets of T cells in patients considered unfit for intensive chemotherapy.11
The aim is to enhance the immune response against the leukemia cells that define AML through precision antibody binding.11,12 This focuses on helping to reshape how T cells recognize and target cancer cells.
While still under investigation, this research reflects a growing focus on novel, selective approaches to modulate immune responses as a potential way to improve outcomes in this challenging blood cancer.
Another step being explored: combining immune strategies with existing treatments
AML is driven by multiple, intersecting biological pathways, meaning durable disease control can be difficult to achieve through a single therapeutic approach.1,2,9 This provides a rationale for exploring immune-targeting strategies in combination with existing standards of care, particularly for people better suited to less intensive treatment approaches.1,2
Looking ahead: the next phase of AML innovation
The growing understanding of the relationship between AML and the immune system reflects a broader and significant shift in how the disease is conceptualized and treated.2,9
Rather than viewing AML solely as a genetic problem at the cellular level, we are now looking at the bigger picture and the surrounding immune environment. As we do, we are uncovering more detail of the immune system’s role in disease persistence and relapse.
At Ipsen, research in immune biology is helping to better understand how future therapeutic strategies in AML may be approached. This is a complex area, but one where the long-term impact could be significant.
This article was funded by Ipsen.
This article is for scientific and educational purposes only and is not intended to provide medical advice, promote any product or imply benefit in any disease area.
©2026 Ipsen Biopharmaceuticals, Inc. All rights reserved.
NON-US-004665 | ALLSC-ALL-008991 | June 2026
References
- Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022;140(12):1345-1377. doi:10.1182/blood.2022016867
- Bakhtiyari M, Liaghat M, Aziziyan F, et al. The role of bone marrow microenvironment (BMM) cells in acute myeloid leukemia (AML) progression: immune checkpoints, metabolic checkpoints, and signaling pathways. Cell Commun Signal. 2023;21(1):252. Published 2023 Sep 21. doi:10.1186/s12964-023-01282-2
- Walter RB, Estey EH. Selection of initial therapy for newly-diagnosed adult acute myeloid leukemia: Limitations of predictive models. Blood Rev. 2020;44:100679. doi:10.1016/j.blre.2020.100679
- Chandra DJ, Alber B, Saultz JN. The Immune Resistance Signature of Acute Myeloid Leukemia and Current Immunotherapy Strategies. Cancers (Basel). 2024;16(15):2615. Published 2024 Jul 23. doi:10.3390/cancers16152615
- Tettamanti S, Pievani A, Biondi A, Dotti G, Serafini M. Catch me if you can: how AML and its niche escape immunotherapy. Leukemia. 2022;36(1):13-22. doi:10.1038/s41375-021-01350-x
- Khaldoyanidi S, Nagorsen D, Stein A, Ossenkoppele G, Subklewe M. Immune Biology of Acute Myeloid Leukemia: Implications for Immunotherapy. J Clin Oncol. 2021;39(5):419-432. doi:10.1200/JCO.20.00475
- Gómez-Llobell M, Peleteiro Raíndo A, Climent Medina J, et al. Immune Checkpoint Inhibitors in Acute Myeloid Leukemia: A Meta-Analysis. Front Oncol. 2022;12:882531. Published 2022 Apr 21. doi:10.3389/fonc.2022.882531
- Liao D, Wang M, Liao Y, Li J, Niu T. A review of efficacy and safety of checkpoint inhibitor for the treatment of acute myeloid leukemia. Front Pharmacol. 2019;10:609. Published 2019 Jun 6. doi:10.3389/fphar.2019.00609
- Vadakekolathu J, Minden MD, Hood T, et al. Immune landscapes predict chemotherapy resistance and immunotherapy response in acute myeloid leukemia. Sci Transl Med. 2020;12(546):eaaz0463. doi:10.1126/scitranslmed.aaz0463
- Soleimani Samarkhazan H, Shafiei FS, Taghinejad Z, et al. The AML immune paradox: decoding escape pathways and pioneering checkpoint, vaccine, and combination strategies. Clin Exp Med. 2025;25(1):240. Published 2025 Jul 9. doi:10.1007/s10238-025-01795-9
- Plyte SE, Winterberg D, Fraudeau M, et al. The MAIT engager platform: rapid generation of several MAIT T-cell engagers with significantly improved safety profile and large therapeutic window. J Immunother Cancer. 2025;13(Suppl 2):A1363. doi:10.1136/jitc-2025-SITC2025.1197
- Plyte S, Fraudeau M, Winterberg D, et al. MAIT Engagers: bispecific antibody-mediated redirection of Mucosal Associated Invariant T-cells to treat solid tumors. Presented at: AACR Annual Meeting; April 10, 2024. Poster 6708