Measurable Residual Disease in
IDH
‐Mutated
AML
: Identifying a Clinically Relevant Threshold for
Guillermo Ramil, Elena Bussaglia, Helena Castellet, Guadalupe Oñate, Ana Garrido, Maite Carricondo, Anna Giné‐Vilalta, Nuria González, Paula San‐José, Rodrigo Martino, María Laura Blanco, Pilar Leoz, Dubraska Ramírez, Clara Martínez, Jorge Sierra, Marta Pratcorona, Josep F. Nomdedeu ABSTRACT
Background
Isocitrate dehydrogenase ( IDH ) mutations are recurrent in acute myeloid leukemia (AML) and represent promising targets for measurable residual disease (MRD) monitoring. However, clinically validated strategies for IDH ‐based MRD assessment remain lacking.
Methods
We evaluated the analytical performance and clinical utility of droplet digital PCR (ddPCR) for IDH mutation monitoring in a single‐center cohort of patients with IDH ‐mutated AML treated with curative intent. Healthy controls were included to characterize low‐level background signals and identify a clinical threshold.
Results
ddPCR showed robust analytical performance, with a limit of detection of 0.01% variant allele frequency (VAF) and strong concordance with NGS. Low‐level IDH mutation signals were frequently detected in healthy individuals and in patients in remission. We identified 0.2% VAF as a candidate threshold for clinically relevant IDH MRD. Using this cutoff, post‐treatment detectable IDH MRD was associated with a higher 2‐year cumulative incidence of relapse (63.6% vs. 20%; p = 0.019) and inferior overall survival (70.6% vs. 92.9%; p = 0.04). Among patients negative by multiparameter flow cytometry, ddPCR identified residual IDH‐ mutated clones in 56% of cases, who showed higher relapse rates than double‐negative patients (50% vs. 0%; p = 0.031).
Conclusions
A 0.2% VAF threshold was associated with clinically distinct outcomes and may provide a useful framework for IDH ‐based MRD assessment in AML.