Jamet Bastien, Shamimeh Ahrari, Sonja Zweegman, Aurore Perrot, Cyrille Hulin, Denis Caillot, Thierry Facon, Xavier Leleu, Karim Belhadj, E. Itti, Lionel Karlin, Clement Bailly, Mark-David Levin, Monique C. Minnema, Caroline Bodet-Milin, Bart de Keizer, Jill Corre, Pieter Sonneveld, Diana Mateus, Philippe Moreau, Cyrille Touzeau, Francoise M Kraeber-Bodere, Thomas Carlier
ABSTRACT: This study aimed to assess the prognostic value of medullary total metabolic tumor volume (mTMTV) derived from fluorodeoxyglucose-positron emission tomography/computed tomography ([18F]FDG-PET/CT) compared with conventional PET-derived features and biological/chromosomal abnormalities in patients with newly diagnosed multiple myeloma (NDMM) treated with daratumumab for induction/consolidation and/or maintenance and enrolled in CASSIOPET, a companion study of CASSIOPEIA, with long-term follow-up. Automated bone/liver CT-based segmentation were applied to the baseline [18F]FDG-PET images, with mTMTV being defined using the median liver background as the cut-off, including focal lesions and diffuse bone marrow (BM) involvement. Both univariate/multivariate Cox and machine learning (ML)-based survival models were performed. A total of 195 patients were included, 81% of them PET-positive. Multivariate analysis demonstrated independent prognostic value of mTMTV for progression-free survival (PFS) (P< .001) and overall survival (OS) (P< .001), complementary to Revised International Staging System (R-ISS) (P = .008 and P< .001, respectively). The ML model confirmed these findings, achieving concordance index of 0.609 and 0.659 and identifying mTMTV as the most informative feature for PFS and OS. Adding R-ISS, BM maximum standardized uptake value (SUVmax) and anemia to mTMTV accounted for >60% of the ML model explanation for PFS and adding R-ISS, the number of focal lesions and BM SUVmax for >60% of the model for OS. Combining R-ISS and mTMTV enabled the creation of 2 new-risk subgroups. In conclusion, this prospective study demonstrated the prognostic relevance of [18F]FDG-PET/CT-based parameters in the initial workup of patients with NDMM in the era of anti-CD38-based therapy. mTMTV was found to have strong independent prognostic value, complementary to R-ISS and refining risk stratification. This trial was registered at www.clinicaltrials.gov as #NCT02541383.