In AML, Immunotherapy Shows Promise to Expand Treatment Toolbox

Immunotherapy offers promising possibilities to improve the treatment of acute myeloid leukemia (AML), but more work needs to be done to understand the homogeneity of the disease and to combat immune escape, according to a new review.

Immunotherapy in medicine

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The report, published in Biomedicine & Pharmacotherapy, details the latest research into the potential role of immunotherapy in treating the disease.

Study investigators explained that the standard therapies for AML are chemotherapy and allogeneic hematopoietic stem cell transplantation. However, they said the significant rate of relapse—and the bleak prognosis for patients who experience relapse—highlights the need for improved treatment options.

“Recent research has increasingly highlighted the notable distinctions between AML tumor microenvironments and those of healthy individuals,” they wrote. “In order to investigate the potential therapeutic mechanisms, this study examines the intricate transformations occurring between leukemic cells and their surrounding cells within the tumor microenvironment [TME] of AML.”

The authors noted that several cells, including hematopoietic stem cells, mesenchymal stem cells, bone marrow stromal cells, and immune cells, interact closely with leukemia cells. They said tumor progression remodels the bone marrow niche and hematopoietic cells, shaping the bone marrow microenvironment and causing it to be significantly different in patients who have AML compared with healthy patients.

“Therefore, identifying differences in the immune microenvironment of patients with AML is crucial for understanding the pathogenesis and chemoresistance of hematological malignancies to provide a theoretical foundation for immunotherapy,” they wrote.

Next, they outlined some of the research leading to a better understanding of the AML immune microenvironment, and the new targets and strategies that research is sparking. They said targeting the tumor microenvironment could lead to new ways to stop tumor progression.

“This not only provides new methods to fight immune escape but also allows for individualized precision medicine,” they wrote.

They then outlined a number of immunotherapies that build on the latest research. They include cancer vaccines, immune checkpoint inhibitors (ICIs), antibody-based immunotherapies, and adoptive T-cell therapies.

In the case of cancer vaccines, although multiple peptide vaccines are in development, the authors said dendritic cell (DC) vaccines have attracted a considerable amount of attention.

“The safety and feasibility of DC vaccines have been validated and are considered promising new treatments, especially helpful in postremission strategies to prevent or delay AML relapse,” they wrote. They said investigators are currently looking at the potential of DC vaccines in combination with other therapies.

Several ICIs are also currently being investigated in AML. These include CTLA-4 inhibitors like ipilimumab (Yervoy; Bristol Myers Squibb) and PD-1/PD-L1 inhibitors like nivolumab (Opdivo; Bristol Myers Squibb) and pembrolizumab (Keytruda; Merck). However, the authors said several other checkpoints are also being investigated and have shown promise.

In terms of antibody-based therapies, the authors said monoclonal antibodies that have been studied so far have not yet shown promise, although bispecific antibodies and antibody-drug conjugates have had stronger performance in trials so far.

They said adoptive T-cell therapies like chimeric antigen receptor T cells have advantages such as long-lasting effects, but they noted that the therapies also have significant downsides, such as the risk of adverse events like cytokine release syndrome. These types of therapies remain under investigation in AML.

Taken together, the authors said these new immunotherapies offer reasons for hope, but they said the diversity of the disease continues to pose a considerable challenge.

“Current research focuses on balancing conventional therapies with immunotherapies,” they said. “Combination therapy strategies have demonstrated encouraging therapeutic effects, although various side effects have been reported and need to be evaluated in clinical trials.”

Reference

Wu Y, Li Y, Gao Y, et al. Immunotherapies of acute myeloid leukemia: rationale, clinical evidence and perspective. Biomed Pharmacother. Published online January 9, 2024. doi:10.1016/j.biopha.2024.116132