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Impact of Minimal Residual Disease Detection by Next-Generation Flow Cytometry in Multiple Myeloma Patients with Sustained Complete Remission after Frontline Therapy.

ABSTRACT: Minimal residual disease (MRD) was monitored in 52 patients with sustained CR (?2 years) after frontline therapy using next-generation flow (NGF) cytometry. 25% of patients initially MRD- reversed to MRD+. 56% of patients in sustained CR were MRD+; 45% at the level of 10^-5; 17% at 10^-6. All patients who relapsed during follow-up were MRD+ at the latest MRD assessment, including those with ultra-low tumor burden. MRD persistence was associated with specific phenotypic profiles: higher erythroblasts' and tumor-associated monocytes/macrophages' predominance in the bone marrow niche. NGF emerges as a suitable method for periodic, reproducible, highly-sensitive MRD-detection at the level of 10^-6.

SUBMITTER: Terpos E

PROVIDER: S-EPMC6924563 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

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Impact of Minimal Residual Disease Detection by Next-Generation Flow Cytometry in Multiple Myeloma Patients with Sustained Complete Remission after Frontline Therapy.

Terpos Evangelos E Kostopoulos Ioannis V IV Kastritis Efstathios E Ntanasis-Stathopoulos Ioannis I Migkou Magdalini M Rousakis Pantelis P Argyriou Alexandra T AT Kanellias Nikolaos N Fotiou Despina D Eleutherakis-Papaiakovou Evangelos E Gavriatopoulou Maria M Ziogas Dimitrios C DC Papanota Aristea-Maria AM Spyropoulou-Vlachou Marilyn M Trougakos Ioannis P IP Tsitsilonis Ourania E OE Paiva Bruno B Dimopoulos Meletios A MA

HemaSphere 20191001 6

Minimal residual disease (MRD) was monitored in 52 patients with sustained CR (≥2 years) after frontline therapy using next-generation flow (NGF) cytometry. 25% of patients initially MRD- reversed to MRD+. 56% of patients in sustained CR were MRD+; 45% at the level of 10<sup>-5</sup>; 17% at 10<sup>-6</sup>. All patients who relapsed during follow-up were MRD+ at the latest MRD assessment, including those with ultra-low tumor burden. MRD persistence was associated with specific phenotypic profil ...[more]

PMID: 31976475

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Project description:BackgroundLimited 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.MethodsMRD 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.FindingsBetween 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).InterpretationThe 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.FundingAmgen, Celgene/Bristol Myers Squibb, Multiple Myeloma Research Foundation.

Dataset Information

Impact of Minimal Residual Disease Detection by Next-Generation Flow Cytometry in Multiple Myeloma Patients with Sustained Complete Remission after Frontline Therapy.

Publications

Impact of Minimal Residual Disease Detection by Next-Generation Flow Cytometry in Multiple Myeloma Patients with Sustained Complete Remission after Frontline Therapy.

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