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Eight-color multiparameter flow cytometry (EuroFlow-NGF) is as sensitive as next-generation sequencing in detecting minimal/measurable residual disease in autografts of patients with multiple myeloma.

ABSTRACT: The prognostic value of minimal/measurable residual disease (MRD) detection in autografts of patients with multiple myeloma (MM) in an autologous stem-cell transplantation setting has been reported. Next-generation flow (NGF) cytometry has lower sensitivity (2 × 10^-6) to detect MRD than next-generation sequencing (NGS) (<10^-6). We compared the clinical value of high-sensitivity NGF (cutoff: <10^-6) and NGS (cutoff: 10^-6) for the detection of MRD in the cryopreserved autografts of 49 patients with newly diagnosed MM. The sensitivity test using frozen/thawed autografts revealed a strong correlation among MRD levels of 5 × 10^-7 and 1 × 10^-4 (r = 0.9997, p < 0.0001) when an adequate number of cells were analyzed. Autograft MRD levels determined using NGF and NGS were highly correlated (r = 0.811, p < 0.0001). MRD-negative patients identified with NGF (cutoff: <10^-6) showed significantly longer progression-free survival (PFS) than MRD-positive patients (p = 0.026). The PFS of MRD-negative patients determined by NGS (cutoff: 10^-6) was similar to that determined by NGF. These results show that the high-sensitivity NGF method can assess MRD in frozen/thawed autografts, and its prognostic value is comparable to that of NGS.

SUBMITTER: Urushihara R

PROVIDER: S-EPMC9928796 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Eight-color multiparameter flow cytometry (EuroFlow-NGF) is as sensitive as next-generation sequencing in detecting minimal/measurable residual disease in autografts of patients with multiple myeloma.

Urushihara Ryota R Takezako Naoki N Yoroidaka Takeshi T Yamashita Takeshi T Murata Ryoichi R Satou Kenji K Nakao Shinji S Takamatsu Hiroyuki H

EJHaem 20230124 1

The prognostic value of minimal/measurable residual disease (MRD) detection in autografts of patients with multiple myeloma (MM) in an autologous stem-cell transplantation setting has been reported. Next-generation flow (NGF) cytometry has lower sensitivity (2 × 10-6) to detect MRD than next-generation sequencing (NGS) (<10-6). We compared the clinical value of high-sensitivity NGF (cutoff: <10-6) and NGS (cutoff: 10-6) for the detection of MRD in the ...[more]

PMID: 36819171

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Project description:BackgroundPredicting outcomes for patients with acute myeloid leukemia (AML) on the basis of pretreatment predictors has been the cornerstone of management. Posttreatment prognostic factors are increasingly being evaluated.MethodsAmong 280 younger patients who were treated with intermediate-dose cytarabine (total ≥ 5 g/m2 ) and idarubicin-based induction chemotherapy and achieved remission, 186 were assessed for minimal residual disease (MRD) with an 8-color multiparameter flow cytometry panel performed on bone marrow specimens with a sensitivity of 0.1% or higher.ResultsOne hundred sixty-six patients had samples available 1 to 2 months after induction at the time of complete remission (CR), and 79% became negative for MRD, with an MRD-negative status associated with an improvement in relapse-free survival (RFS; P = .0002) and overall survival (OS; P = .0002). One hundred sixteen were evaluated for their MRD status during consolidation, and 86% were negative, with an MRD-negative status associated with a significant improvement in RFS (P < .0001) and OS (P < .0001). Sixty-nine patients were evaluated for their MRD status after completion of all therapy, and 84% were negative, with an MRD-negative status associated with an improvement in RFS (P < .0001) and OS (P < .0001). In a multivariate analysis including age, cytogenetics, response (CR vs CR with incomplete platelet recovery/incomplete blood count recovery), and MRD, achieving an MRD-negative status was the most important independent predictor of RFS and OS at response (P = .008 and P = .0008, respectively), during consolidation (P < .0001 for both), and at the completion of therapy (P < .0001 and P = .002, respectively).ConclusionsAchieving an MRD-negative status according to multiparameter flow cytometry is associated with a highly significant improvement in the outcomes of younger patients with AML receiving cytosine arabinoside plus idarubicin-based induction and consolidation regimens. Cancer 2017;123:426-435. © 2016 American Cancer Society.

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

Eight-color multiparameter flow cytometry (EuroFlow-NGF) is as sensitive as next-generation sequencing in detecting minimal/measurable residual disease in autografts of patients with multiple myeloma.

Publications

Eight-color multiparameter flow cytometry (EuroFlow-NGF) is as sensitive as next-generation sequencing in detecting minimal/measurable residual disease in autografts of patients with multiple myeloma.

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