Dynamic on-treatment prognosis refinement in molecularly defined lower-risk myelofibrosis

Risk stratification in myelofibrosis (MF) is increasingly shaped by molecularly informed tools. MIPSS70 and MYSEC‑mPM/MYSEC‑kmPM have reclassified a substantial proportion of patients previously considered lower risk by clinical scores. Whether early‑treatment dynamic models retain prognostic value within molecularly annotated cohorts remains unknown. We evaluated RR6 and iRR6 in 197 MF patients classified as intermediate‑1 risk by MIPSS70 (92 PMF) or MYSEC‑mPM/kmPM (105 SMF; 85 evaluable for kmPM). High‑molecular‑risk variants were detected in 56.5% of PMF and 46.7% of SMF, while “UTS” mutations occurred in 31.5% and 15.2%, respectively. Both MIPSS70 and MYSEC‑mPM showed prognostic discrimination at ruxolitinib start (PMF: 5‑year OS 69.9% vs 40.8%; SMF: 74.3% vs 33.7%). RR6 failed to stratify survival within molecularly lower‑risk patients. Conversely, iRR6 identified clinically meaningful risk groups: in PMF (n=65), 5‑year OS was 100% (low), 87.7% (intermediate), and 54.8% (high) (p=0.033); in SMF (n=73), 100%, 81.4%, and 60.4%, respectively (p=0.045). Molecular scores guide baseline prognosis, while the iRR6 provides complementary early‑dynamic risk refinement during ruxolitinib therapy.