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

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Abstract
The CASSIOPEIA trial demonstrated superior progression-free survival (PFS) with the addition of daratumumab to bortezomib, thalidomide, and dexamethasone (D-VTd) induction/consolidation, and with daratumumab maintenance vs observation in transplant-eligible patients with newly diagnosed multiple myeloma (NDMM). The companion study, CASSIOPET, assessed the prognostic value of premaintenance (PM) positron emission tomography (PET)/computed tomography (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 bortezomib, thalidomide, and dexamethasone (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 (P = .019) and a major trend of prolonged OS (P = .056). In univariate analysis, patients who achieved both PET and MFC negativity were found to have a better PFS (P < .0001) than those who had at least 1 positive result. In daratumumab-treated patients, PM PET negativity was associated with prolonged PFS and OS in univariate analysis (P = .0023 and P = .033, respectively), and double MFC and PET negativity was independently associated with PFS by multivariate analysis (P = .0006). This study confirms the prognostic relevance of a PM PET response in patients with NDMM treated with daratumumab in addition to MRD detection by MFC at the BM level. This trial was registered at ww.clinicaltrials.gov as #NCT02541383.

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