MRD and Biomarkers

Category: MRD and Biomarkers

Dynamic Changes in Cytogenetic Abnormalities Detected by Serial FISH Predict MRD Status and Outcomes in Multiple Myeloma

(PA-202) Dynamic Changes in Cytogenetic Abnormalities Detected by Serial FISH Predict MRD Status and Outcomes in Multiple Myeloma

Wednesday, September 17, 2025

JZ

Jieqiong Zhou

PhD candidate
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College

Introduction: Cytogenetic abnormalities (CAs) in multiple myeloma (MM) are known to evolve over time, with clonal shifts commonly observed at relapse. However, few studies have systematically examined the dynamic changes in CAs detected by fluorescence in situ hybridization (FISH) prior to relapse. Although FISH is a standard diagnostic tool at baseline, its role in longitudinal monitoring before disease progression has been underexplored.

Methods: We retrospectively analyzed 588 MM patients who underwent multiple FISH tests before relapse. We investigated the evolution of high-risk cytogenetic abnormalities (HRCAs) and their association with minimal residual disease (MRD) dynamics and patient outcomes. Patients were stratified based on baseline and follow-up FISH results, and corresponding MRD response patterns were assessed.

Results: Among patients with progression-free survival (PFS) >3 years, there was no significant survival difference between baseline high-risk and standard-risk groups. However, dynamic FISH assessments revealed prognostically relevant patterns: patients whose HRCAs converted from positive to negative (HR→SR) were more likely to achieve and sustain MRD negativity, whereas patients who converted from negative to positive (SR→HR) had a lower MRD-negative rate and shorter duration of MRD response. Importantly, clonal expansion of HRCAs was observed before MRD progression, indicating that cytogenetic shifts may precede molecular relapse.

Conclusions: Our findings demonstrate that longitudinal FISH testing captures cytogenetic evolution that correlates with MRD dynamics and clinical outcomes. Compared to single-timepoint FISH, dual FISH assessments provide greater prognostic value and may guide earlier clinical interventions. These results support incorporating a second FISH test before relapse, not just at diagnosis or after relapse, to improve risk stratification and disease monitoring in MM.