Measurable Residual Disease Shows Promise as Survival Predictor in Acute Myeloid Leukemia
A new study suggests measurable residual disease (MRD) after initial treatment may serve as a reliable indicator of long-term survival for patients with acute myeloid leukemia (AML), potentially accelerating the development and approval of new therapies.
ORLANDO — Researchers presented findings at the ASH Annual Meeting and Exposition indicating that monitoring MRD levels after induction therapy could offer an earlier assessment of treatment effectiveness in AML, a historically difficult-to-cure blood cancer. “AML remains a difficult disease to cure. There have been recent advancements in the past couple of years with new drugs, FLT3 and IDH inhibitors, but it takes a long time for these drugs to be implemented in clinic,” explained a senior researcher during a press briefing. “We are therefore looking for alternative earlier markers that we can use to assess if treatment is working for patients.”
The study, led by Jesse Tettero, MD, PhD, of Virginia Tech FBRI Cancer Research Center, involved a pooled analysis of data from seven randomized trials conducted in Europe, encompassing 1,858 adult patients with AML. Researchers assessed MRD levels following two cycles of intensive chemotherapy, comparing the results to long-term overall survival (OS) data based on FDA criteria.
“We were looking for measurable residual disease as a surrogate endpoint because of its great prognostic value and also because it is already a surrogate in other diseases, such as acute lymphoblastic leukemia and multiple myeloma,” Tettero stated. The results demonstrated a strong correlation between MRD response and OS across all trials examined (R² = 0.91; 95% CI, 0.56-1).
Notably, the correlation between MRD response and OS was significantly higher among patients who did not undergo a stem cell transplant (R² = 0.99; 95% CI, 0.94-1) compared to those who did (R² = 0.54; 95% CI, 0-1). “There is some caution that should be noted when interpreting these data,” Tettero cautioned. “The lower confidence interval is 0.56 but the FDA requires 0.6. We could focus on the non-transplanted patients where the R² becomes 0.99, showing that MRD is strongly correlated with survival within these trials. We likely think that is because transplant occurs after MRD measurement. Most likely, the transplant mitigates MRD risk.”
These findings have significant implications for clinical trial design and drug approval processes. If the FDA were to recognize MRD as a valid surrogate endpoint, it could potentially expedite the approval of effective AML therapies. “This would enable potential accelerated approval,” Tettero said. “If supported, this could lead to smarter and faster clinical trials for patients.”
The study did have limitations. Researchers acknowledged that the analysis included only patients who received intensive chemotherapy and that all trials were conducted within a European population. “It is important to note that this type of research is only possible when we all truly work together internationally to get things done,” Tettero emphasized.
For more information, Jesse Tettero, MD, PhD, can be reached at [email protected].
Source: Tettero J, et al. Abstract 343. Presented at: ASH Annual Meeting and Exposition; Dec. 6-9, 2025; Orlando.
Disclosure: Tettero reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
