Prognostic value of premaintenance FDG PET/CT response in patients with newly diagnosed myeloma from the CASSIOPEIA trial.

The CASSIOPEIA trial (NCT02541383) demonstrated superior progression-free survival (PFS) with the addition of daratumumab to bortezomib, thalidomide, and dexamethasone (D-VTd) induction/consolidation and with daratumumab maintenance versus observation in transplant-eligible newly diagnosed multiple myeloma (NDMM) patients. The companion study, CASSIOPET, assessed the prognostic value of pre-maintenance (PM) PET/CT response based on the standardized Deauville score on PFS and overall survival (OS) in addition to bone marrow (BM) minimal residual disease (MRD) detection by multiparameter flow cytometry (MFC) at 10-5 level. PM PET/CT was available for 225 patients: 112 patients treated with daratumumab after D-VTd (59) or VTd (53) and 113 patients followed by observation after D-VTd (56) or VTd (57). At PM, 92% of the 175 baseline PET-positive patients achieved PET-negativity, with a longer PFS in univariate analysis (HR, 0.48; P = 0.019) and a major trend of prolonged OS (HR, 0.37; P = 0.056). In univariate analysis, patients who achieved both PET and MFC negativity were found to have a better PFS (HR, 0.39; P<0.0001) than those who had at least one positive result. In daratumumab-treated patients, PM PET-negativity was associated with prolonged PFS and OS in univariate analysis (HR, 0.35; P = 0.0023 and HR, 0.32, P = 0.033, respectively) and double MFC and PET-negativity was independently associated with PFS by multivariate analysis (HR, 0.39, P = 0.0006). This study confirms the prognostic relevance of a PM PET response in NDMM patients treated with daratumumab in addition to MRD detection by MFC at the BM level.