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

Stefania Oliva, Elisa Genuardi, Laura Paris, Mattia D'Agostino, Jennifer Rogers, Delia Rota-Scalabrini, Allison P Jacob, Francesca Patriarca, Mario Luppi, Paola Bertazzoni, Cristina Velluti, Andrea Capra, Elona Saraci, Marco Rossi, Alessandro Allegra, Roberto Mina, Massimo Gentile, Ilan R Kirsch, Angelo Belotti, Michele CavoBenedetto Bruno, Pellegrino Musto, Mario Boccadoro, Elena Zamagni, Francesca Gay

Risultato della ricerca: Contributo in rivistaArticolo in rivista

Abstract

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.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaEClinicalMedicine
Volume60
DOI
Stato di pubblicazionePubblicato - 2023

Keywords

  • Autologous stem-cell transplantation (ASCT)
  • Minimal residual disease (MRD)
  • Next-generation sequencing (NGS)
  • Newly diagnosed multiple myeloma (NDMM)
  • Multiparameter flow cytometry (MFC)

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