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

• Published in: EClinicalMedicine Vol. 60; p. 102016
• Main Authors: Oliva, Stefania, Genuardi, Elisa, Paris, Laura, D'Agostino, Mattia, Rogers, Jennifer, Rota-Scalabrini, Delia, Jacob, Allison P., Patriarca, Francesca, Luppi, Mario, Bertazzoni, Paola, Velluti, Cristina, Capra, Andrea, Saraci, Elona, Rossi, Marco, Allegra, Alessandro, Mina, Roberto, Gentile, Massimo, Kirsch, Ilan R., Belotti, Angelo, Cavo, Michele, Bruno, Benedetto, Musto, Pellegrino, Boccadoro, Mario, Zamagni, Elena, Gay, Francesca
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.06.2023; Elsevier
• Subjects: Autologous stem-cell transplantation (ASCT); Minimal residual disease (MRD); Multiparameter flow cytometry (MFC); Newly diagnosed multiple myeloma (NDMM); Next-generation sequencing (NGS); Newly diagnosed multiple myeloma (NDMM); Minimal residual disease (MRD); Multiparameter flow cytometry (MFC); Next-generation sequencing (NGS); Autologous stem-cell transplantation (ASCT)
• ISSN: 2589-5370; 2589-5370
• DOI: 10.1016/j.eclinm.2023.102016

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. 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. 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). 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. Amgen, Celgene/Bristol Myers Squibb, Multiple Myeloma Research Foundation.