Prognostic impact of focal lesion location and persistence in multiple myeloma: insights from serial PET/DWI imaging.

abstractMultiple myeloma (MM) is a heterogeneous disease exemplified by focal lesions (FLs), densely populated nodules whose number and persistence during treatment predict poor outcome. However, the prognostic role of FL location and the relationship between FLs at different time points remain underexplored, although they may provide critical clues to disease evolution and resistance mechanisms. We analyzed positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DWI) scans from 243 patients with MM enrolled in total therapies at baseline, after autologous stem cell transplant (ASCT), and every 6 to 12 months thereafter until relapse or last follow-up. Baseline FLs in the humerus or femur were associated with poor prognosis. Although rare, residual PET-positive FLs after ASCT identified patients with worse outcomes. One-third of patients had residual FLs on DWI after ASCT, which also correlated with poor prognosis. Even FLs that resolved after the second ASCT in patients who underwent tandem ASCTs retained adverse prognostic significance, highlighting the limitations of late imaging in high-risk patients. Patients who achieved both minimal residual disease (MRD) and imaging negativity after ASCT had the best outcomes. Conversely, MRD-negative patients with FLs had as poor outcomes as double-positive patients. Residual FLs persisting to relapse were predominantly observed in early relapse cases, and resolved FLs frequently recurred at the same or nearby sites, suggesting limited imaging sensitivity for detection of focal resistant cells. Taken together, this study identifies long bone FLs as a risk factor, and underscores the value of serial imaging and the urgent need for alternative treatment strategies for patients with persistent FLs.