Prognostic value of simultaneous [¹⁸F]FDG-PET/MRI in refractory multiple myeloma treated with anti-BCMA CAR T

The aims of this study were to assess the prognostic value for progression-free survival (PFS) and the diagnostic value (detection rate of multiple myeloma [MM]-related medullary and extra-medullary disease) of whole-body simultaneous [¹⁸F]fluorodeoxyglucose-positron emission tomography coupled with magnetic resonance imaging (WB[¹⁸F]FDG-PET/MRI) performed before and after idecabtagene-vicleucel (ide-cel) therapy in patients with triple-class (or more) relapsed/refractory multiple myeloma (RRMM). A total of 73 patients were prospectively enrolled in this monocentric cohort, and 72 of them underwent WB[¹⁸F]FDG-PET/MRI imaging before ide-cel (after personalized bridging therapy). Overall, active disease was detected in 64/72 patients (89%). Multivariate analyses showed that the presence of diffuse bone marrow involvement (BMI) pattern on PET (hazard ratio [HR]: 2.65; 95% CI: 1.16-6.1, P = 0.02) or MRI (HR: 2.69; 95% CI: 1.28-5.66, P = 0.009) was associated with shorter PFS. A total of 66 patients underwent [¹⁸F]FDG-PET/MRI for response to ide-cel therapy assessment. Diffusion-weighted MRI (DW-MRI) detected residual disease (response assessment category [RAC]2 or higher according to MY-RADS) in 9/66 patients (14%) and PET (no complete metabolic response according to Deauville score) in 7/66 patients (11%). Overall, [¹⁸F]FDG-PET/MRI increased residual disease detection to 13 of 66 patients (20%). Patients with residual disease on DW-MRI (RAC2 or higher) had shorter PFS (HR: 4.11; 95% CI: 1.8-9.4; P < 10^-3) than those without (RAC1). Achieving at least a partial metabolic response on PET significantly improved the PFS (P = 0.0046) as well. The combination of [¹⁸F]FDG-PET and DW-MRI enabled the identification of three distinct risk groups, including a very high-risk group defined by both MRI and PET positivity.