%0 Journal Article
%T Prospective evaluation of minimal residual disease in the phase II FORTE trial: a head-to-head comparison between multiparameter flow cytometry and next-generation sequencing.
%A Oliva S
%A Genuardi E
%A Paris L
%A D'Agostino M
%A Rogers J
%A Rota-Scalabrini D
%A Jacob AP
%A Patriarca F
%A Luppi M
%A Bertazzoni P
%A Velluti C
%A Capra A
%A Saraci E
%A Rossi M
%A Allegra A
%A Mina R
%A Gentile M
%A Kirsch IR
%A Belotti A
%A Cavo M
%A Bruno B
%A Musto P
%A Boccadoro M
%A Zamagni E
%A Gay F
%J EClinicalMedicine
%V 60
%N 0
%D 2023 Jun
%M 37396800
%F 17.033
%R 10.1016/j.eclinm.2023.102016
%X <B>UNASSIGNED: </B>Limited data are available on the concordance between multiparameter flow cytometry (MFC) and next-generation sequencing (NGS) for minimal residual disease (MRD) detection in a large trial for multiple myeloma (MM) patients.<BR><B>UNASSIGNED: </B>MRD was explored in the FORTE trial for transplant-eligible MM patients randomised to three carfilzomib-based induction-intensification-consolidation treatments and carfilzomib-lenalidomide (KR) vs R maintenance. MRD was assessed by 8-colour 2nd-generation flow cytometry in patients with ≥very good partial response before maintenance. NGS was performed in case of suspected complete response (CR) in a correlative subanalysis. Biological/prognostic concordance between MFC and NGS, conversion to MRD negativity during maintenance, and 1-year/2-year sustained MRD negativity were explored.<BR><B>UNASSIGNED: </B>Between September 28, 2015 and December 22, 2021, 2020 samples were available for MFC and 728 for the simultaneous MFC/NGS correlation in the "suspected CR population". Median follow-up was 62 months. Biological agreement was 87% at the 10-5 and 83% at the 10-6 cut-offs. A remarkable prognostic concordance was observed: hazard ratios in MFC-MRD and NGS-MRD-negative vs -positive patients were 0.29 and 0.27 for progression-free survival (PFS) and 0.35 and 0.31 for overall survival, respectively (p < 0.05). During maintenance, 4-year PFS was 91% and 97% in 1-year sustained MFC-MRD-negative and NGS-MRD-negative patients (10-5), respectively, and 99% and 97% in 2-year sustained MFC-MRD-negative and NGS-MRD-negative patients, regardless of treatment received. The conversion rate from pre-maintenance MRD positivity to negativity during maintenance was significantly higher with KR vs R both by MFC (46% vs 30%, p = 0.046) and NGS (56% vs 30%, p = 0.046).<BR><B>UNASSIGNED: </B>The significant biological/clinical concordance between MFC and NGS at the same sensitivity suggests their possible use in the evaluation of one of the currently strongest predictors of outcome.<BR><B>UNASSIGNED: </B>Amgen, Celgene/Bristol Myers Squibb, Multiple Myeloma Research Foundation.