TY - JOUR
T1 - 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
AU - Oliva, Stefania
AU - Genuardi, Elisa
AU - Paris, Laura
AU - D'Agostino, Mattia
AU - Rogers, Jennifer
AU - Rota-Scalabrini, Delia
AU - Jacob, Allison P
AU - Patriarca, Francesca
AU - Luppi, Mario
AU - Bertazzoni, Paola
AU - Velluti, Cristina
AU - Capra, Andrea
AU - Saraci, Elona
AU - Rossi, Marco
AU - Allegra, Alessandro
AU - Mina, Roberto
AU - Gentile, Massimo
AU - Kirsch, Ilan R
AU - Belotti, Angelo
AU - Cavo, Michele
AU - Bruno, Benedetto
AU - Musto, Pellegrino
AU - Boccadoro, Mario
AU - Zamagni, Elena
AU - Gay, Francesca
PY - 2023
Y1 - 2023
N2 - Background: 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. Methods: 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. Findings: 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). Interpretation: 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. Funding: Amgen, Celgene/Bristol Myers Squibb, Multiple Myeloma Research Foundation.
AB - Background: 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. Methods: 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. Findings: 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). Interpretation: 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. Funding: Amgen, Celgene/Bristol Myers Squibb, Multiple Myeloma Research Foundation.
KW - Autologous stem-cell transplantation (ASCT)
KW - Minimal residual disease (MRD)
KW - Next-generation sequencing (NGS)
KW - Newly diagnosed multiple myeloma (NDMM)
KW - Multiparameter flow cytometry (MFC)
KW - Autologous stem-cell transplantation (ASCT)
KW - Minimal residual disease (MRD)
KW - Next-generation sequencing (NGS)
KW - Newly diagnosed multiple myeloma (NDMM)
KW - Multiparameter flow cytometry (MFC)
UR - http://hdl.handle.net/10807/305364
U2 - 10.1016/j.eclinm.2023.102016
DO - 10.1016/j.eclinm.2023.102016
M3 - Article
SN - 2589-5370
VL - 60
SP - N/A-N/A
JO - EClinicalMedicine
JF - EClinicalMedicine
ER -