A groundbreaking study presented by Noella Collado-Gisbert at EHA has shed new light on the prognostic importance of measurable residual disease (MRD) kinetics in multiple myeloma (MM), revealing insights that could influence future treatment strategies and clinical trial design.
The research aimed to better define MRD kinetics and resistance, using next-generation flow (NGF) to track 2,625 MRD assessments in 539 patients enrolled in the GEM2012-2014 and GEM2017FIT trials, with validation in a separate real-world cohort of 249 Greek patients. Patients were stratified into three groups: sustained undetectable MRD, positive/stable MRD, and positive/increasing MRD. Strikingly, the six-year progression-free survival (PFS) rates were 83%, 74%, and just 11% respectively, highlighting MRD kinetics as a powerful predictor of long-term outcomes.
Further analysis of MRD cells showed progressive genetic evolution from diagnosis through post-transplant stages, with distinct transcriptional signatures linked to immune response pathways. Alterations in immune cell composition were also observed, suggesting an interplay between tumour cells and the immune microenvironment in MRD persistence.
Using the MIcγ1 huCRBN immunocompetent mouse model, researchers tested early interception of MRD with anti-BCMA CAR T-cell therapy. Treatment at the MRD stage significantly prolonged survival compared to therapy administered at relapse (12.2 vs 9.5 months; p<.0001).
This study not only establishes MRD kinetics as the most relevant prognostic factor in MM but also provides a strong preclinical rationale for early therapeutic intervention at the MRD stage to improve patient outcomes.
Helena Bradbury, EMJ
Reference
Collado-Gisbert N et al. Abstract S186. EHA 2025; 12-15 June, Milan, Italy.
