The improved understanding of Acute Myeloid Leukemia (AML) pathobiology has led to significant advances in treatment options. AML is a highly heterogeneous disease, with clinical, morphological, cytogenetic, and molecular variability, which is crucial for developing targeted therapies within different subgroups.

The "7 + 3" regimen (7 days of cytarabine and 3 days of daunorubicin) remains the standard, but its long-term efficacy is limited, with remission rates below 40% in younger, fit patients. In contrast, for older patients or those unsuitable for intensive chemotherapy, median survival is approximately 9 months, and 5-year survival rates are under 10%. Treatment strategies are typically tailored, with intensive chemotherapy preferred for younger/fit patients, and low-intensity therapies for older/unfit patients.

This section reviews emerging targeted treatment options.

Gemtuzumab ozogamicin (GO), a CD33-targeted ADC combined with high-dose cytarabine, has increased survival rates from 50% to 75-80%. IMGN779, a novel anti-CD33 ADC, is highly effective against AML cells, including those with adverse molecular abnormalities, and its sensitivity is correlated with CD33 expression levels.

AVE9633, another anti-CD33-maytansin conjugate, has shown promising results in Phase I trials with relapsed/refractory AML patients. Targeting CD123 with ADCs and exploring NK cell therapies offer hope for AML with measurable residual disease (MRD) or high-risk forms.

Bispecific T-cell engagers (BiTEs), such as AMG330 and AMG673, redirect T-cells or NK cells to AML cells, yielding a 20-30% response rate, though they are associated with significant side effects like cytokine release syndrome. These therapies may benefit MRD-positive AML patients in remission. T-cell immunotherapies, including flotetuzumab (FLZ), enhance T-cell activation and MHC-independent killing of AML cells, showing promise in overcoming chemotherapy resistance.

Immune checkpoint inhibitors targeting PD-1/PD-L1 are being explored in AML and Myelodysplastic Syndromes (MDS). Preclinical studies suggest potential benefits, but challenges remain in identifying biomarkers and optimizing combination therapies. Magrolimab, an anti-CD47 monoclonal antibody, has shown a 71% response rate and 45% complete remission (CR) when combined with azacitidine in TP53-mutant AML.

The success of CAR-T cell therapies in hematologic cancers has sparked interest in applying this approach to AML. Preclinical studies show that CAR-T cells targeting AML surface proteins, such as CD33 and CD123, can effectively eliminate AML cells. However, off-target toxicity due to antigen expression on healthy stem cells remains a concern.

Natural killer (NK) cells are being explored as an alternative to allogeneic cell therapies. NK cells can recognize and kill AML cells without causing graft-versus-host disease or cytokine release syndrome, offering a potentially safer treatment approach.

In conclusion, with accumulating data, new treatment standards are being developed for AML, particularly for younger and older patients, including induction, consolidation, hematopoietic stem cell transplantation (HSCT), and maintenance therapy.