Tehran University of Medical Sciences International Journal of Hematology-Oncology and Stem Cell Research 2008-2207 20 2 2026 06 29 159 173 Homdutt Sharma Department of Hematology, All India Institute of Medical Sciences, Delhi, India Pradeep Kumar Department of Hematology, All India Institute of Medical Sciences, Delhi, India Neelabh Nayan Department of Hematology, All India Institute of Medical Sciences, Delhi, India Rakesh Kumar Department of Nuclear Medicine, All India Institute of Medical Sciences, Delhi, India Tulika Seth Department of Hematology, All India Institute of Medical Sciences, Delhi, India Rishi Dhawan Department of Hematology, All India Institute of Medical Sciences, Delhi, India Jasmita Dass Department of Hematology, All India Institute of Medical Sciences, Delhi, India Mukul Aggarwal Department of Hematology, All India Institute of Medical Sciences, Delhi, India Ganesh Viswanathan Department of Hematology, All India Institute of Medical Sciences, Delhi, India Richa Chauhan Department of Hematology, All India Institute of Medical Sciences, Delhi, India Manoranjan Mahapatra Department of Hematology, All India Institute of Medical Sciences, Delhi, India 2025 07 04 2026 04 11 Background: Multiple myeloma is a heterogeneous malignancy with patchy bone marrow involvement, often leading to discrepancies between biochemical and imaging-based response assessments. Site-specific bone marrow biopsies may miss focal disease, while FDG PET/CT detects metabolically active lesions, and the two approaches offer complementary prognostic value. Materials and Methods: This prospective study included 44 newly diagnosed multiple myeloma patients. The primary aim was to assess the correlation between biochemical and PET/CT responses at six months post-induction. A secondary objective was to evaluate the impact of PET/CT response on 12-month event-free survival (EFS). Results: The median age was 55.5 years. At baseline, more than 3 focal lesions and extramedullary disease (EMD) were observed in 61.4% and 34.1% of patients, respectively. After six months of induction therapy, 86.3% achieved at least a very good partial response (≥VGPR) biochemically, but 52.3% remained PET/CT-positive. Baseline >3 focal lesions and EMD significantly predicted persistent PET/CT positivity (p = 0.004). Notably, 50% of patients with ≥VGPR still showed PET/CT-positive findings. At 12 months, 75% of patients who experienced clinical events had been PET/CT-positive at six months, compared with 47.2% of those without events (p = 0.245). The 12-month event-free survival was lower in the PET/CT-positive group (73.9% vs. 90.4%, p = 0.182), though this difference was not statistically significant. Conclusion: 18-FDG PET/CT can detect residual disease not captured by biochemical markers, highlighting the value of combined assessment in multiple myeloma. Baseline >3 focal lesions and EMD predicted persistent PET/CT positivity. Although PET/CT positivity at six months showed a trend toward worse 12-month EFS, larger studies are needed to confirm its prognostic significance. https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/view/2477 https://ijhoscr.tums.ac.ir/index.php/ijhoscr/article/download/2477/1132