MRD-Guided Adaptation and the Challenge of Standardizing Response-Based Therapy

This segment centers on MRD as a pivotal tool for guiding therapy in AML. The panel discusses how MRD, once an investigational concept, is rapidly becoming central to treatment planning, particularly as outcomes improve with targeted agents and combination regimens. The clinicians emphasize that tailoring therapy based on biological disease activity, rather than simply tolerability, represents the next major step in AML care.

They note that MRD-guided strategies could allow escalation for patients with persistent disease or de-escalation for those who achieve deep remission, reducing treatment-related toxicity without compromising cure potential. However, they acknowledge that the field has not yet reached uniformity: MRD assays vary across institutions, and many platforms lack harmonization in sensitivity, thresholds, and interpretation. Some mutations, like NPM1 mutations or KMT2A rearrangements, lend themselves to reliable MRD monitoring, whereas others do not. This inconsistency complicates efforts to standardize adaptive treatment algorithms.

Panelists express enthusiasm about emerging next-generation MRD technologies capable of detecting molecular relapse earlier than traditional methods. These include more sensitive sequencing approaches and novel assays targeting mutations with high specificity. Such tools may eventually clarify ambiguous cases and support more precise transplant decisions. Still, the speakers caution that despite compelling early results, MRD-driven escalation or de-escalation requires prospective validation.

The segment concludes by positioning MRD as essential to advancing AML care but acknowledges that practical implementation is still evolving. Until standardized MRD thresholds and response-adapted protocols are established, clinicians must interpret MRD results within a broader clinical framework. The panel is optimistic that in the next few years, MRD-based personalization will transform how AML induction, consolidation, and maintenance strategies are chosen.