Precision Medicine Era Generates New Options, Questions in AML

Cytogenetic advances, next-generation sequencing (NGS), and novel targeted therapies have helped to usher in an era of precision medicine in the treatment of acute myeloid leukemia (AML), but challenges remain in translating the latest advances into regular clinical practice, according to a new review.

Historically, the treatment of AML was based on uniform chemotherapy regimens and stem cell transplantation, explained the authors. However, that treatment framework was largely ineffective, particularly for older or unfit patients, they explained. More recently, advances in genomic profiling have allowed clinicians to move away from a one-size-fits-all approach and more closely design treatments to match individual cases. In particular, investigators have shown that treatment can be optimized when certain actionable mutations are identified, including FLT3, NPM1, IDH1/2, and TP53. In addition, the metric of measurable residual disease (MRD) has proven to be a meaningful tool to assess and guide care.

In the new review article, which was published in the journal Oncology, the authors offer an approach to selecting the best first-line therapy, share a practical guide for interpreting MRD to manage patients, and offer insights into the remaining challenges and limitations of the new paradigm.¹

Although the days of uniform chemotherapy are over, they said patient fitness continues to play an important role in choosing an upfront therapy. Fitness, along with disease biology, can help determine whether to start with a high- or low-intensity therapy. The investigators added, however, that such determinations are not always clear-cut.

“An ongoing area of debate in older patients is the optimal frontline platform when both disease biology and physiologic fitness are borderline between intensive and low-intensity options,” they wrote.

Next, the investigators outlined some of the potential therapeutic options for various disease profiles, adding that MRD is a crucial tool in subsequent decision-making.

“MRD results, together with initial risk stratification, inform whether the patient should proceed to curative allogeneic transplant or continue with chemotherapy-based consolidation,” they said.

The authors said patients with adverse-risk AML generally ought to proceed to transplantation in their first complete remission, if a donor is available. In presenting their framework for the use of MRD in the clinic, they said the key timepoints for MRD assessment include post induction and post consolidation, before transplant, and serially for posttherapy and posttransplant monitoring when an actionable marker exists.

One important reason for the continual monitoring, they said, is the significant risk of disease recurrence or refractory disease. Such patients similarly warrant individualized treatment planning, the investigators said. They added that targeted salvage options and emerging new agents offer promising new strategies for long-term remission.² In cases where initial remissions are short or in refractory cases, clinical trials for new agents or cellular therapies may offer an avenue for hope, they said.

The authors closed their review by highlighting some of the key challenges and barriers related to AML therapy. They noted that disease heterogeneity and clonal evolution remain major problems, forcing clinicians to deal with moving targets.

“Relpased AML often harbors new mutations that are not present at diagnosis, complicating subsequent treatment choices,” they noted.

The authors added that the tools used to guide optimal care, including NGS panels and MRD assays, can be difficult to access, particularly in low- and middle-income countries.

“Pragmatic stepwise approaches—prioritizing rapid karyotyping/FLT3 testing, targeted PCR (polymerase chain reaction) for common actionable lesions, and referral networks for MRD/NGS—may help narrow inequities while broader infrastructure and financing strategies are developed,” they wrote.

Other questions and controversies include how best to sequence therapies, how to incorporate new technologies like machine learning, and even how to modify lifestyle and environmental factors that may contribute to AML risk.

Ultimately, the authors said the current paradigm is one of myriad strategies and tools to fine-tune treatment choices. They said combining conventional modalities with targeted therapies and MRD-adaptive interventions can give patients the highest chance of success.

“Such a strategy embodies the essence of precision medicine in AML,” they said, “that is, the right therapy for the right patient at the right time, based on the leukemia’s unique genetic profile and real-time response indicators.”

References

1. Al-Shibly R, Benkhadra M, Yassin MA. Transforming acute myeloid leukemia care through precision medicine: integrating genomic profiling, measurable residual disease, and targeted therapies. Oncology. Published online March 30, 2026. doi:10.1159/000551702
2. Wysota M, Konopleva M, Mitchell S. Novel therapeutic targets in acute myeloid leukemia (AML). Curr Oncol Rep. 2024;26(4):409-420. doi:10.1007/s11912-024-01503-y