FDG-PET medullary total tumor volume highlights high-risk patients with newly diagnosed multiple myeloma in CASSIOPEIA trial.

Clinical Snapshot

Key Findings

• P Value: P<0.001 for both PFS and OS

• Effect Size: Complementary to R-ISS staging system with machine learning concordance indices of 0.609 (PFS) and 0.659 (OS)

• Primary Outcome: Independent prognostic value of mTMTV for both progression-free survival and overall survival

• Nnt Or Sensitivity: mTMTV identified as most informative feature in ML models, accounting for >60% of model explanation when combined with clinical factors

• Confidence Interval: Not reported in abstract

Clinical Application

Highly feasible - FDG-PET/CT already standard staging investigation for myeloma in Australian practice Directly applicable to Australian practice where FDG-PET/CT is Medicare-funded for myeloma staging and daratumumab is PBS-listed for eligible patients. Could inform treatment intensity decisions and clinical trial stratification Newly diagnosed multiple myeloma patients eligible for intensive therapy with daratumumab-based regimens

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.

References

1. 1.Jamet, B., Ahrari, S., Zweegman, S., Perrot, A., Hulin, C., Caillot, D., Facon, T., Leleu, X., Belhadj, K., Itti, E., Karlin, L., Bailly, C., Levin, M. D., Minnema, M. C., Bodet-Milin, C., de Keizer, B., Corre, J., Sonneveld, P., Mateus, D., Moreau, P., Touzeau, C., Kraeber-Bodéré, F., & Carlier, T. (2026). FDG-PET medullary total tumor volume highlights high-risk patients with newly diagnosed multiple myeloma in CASSIOPEIA trial. Blood Advances. https://doi.org/10.1182/bloodadvances.2025019465