MRD detection in multiple myeloma: comparison between MSKCC 10-color single-tube and EuroFlow 8-color 2-tube methods

Roshal, Mikhail; Flores‐Montero, Juan; Gao, Qi; Koeber, Maesa; Wardrope, Jessica; Durie, Brian G.M.; Doğan, Ahmet; Órfão, Alberto; Landgren, Ola

doi:10.1182/bloodadvances.2016003715

Cited by 91 publications

(71 citation statements)

References 17 publications

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“…With a sensitivity of 10 −5 for NGS, all four patients were MRD positive. This limitation with the sensitivity threshold has now been overcome, since high‐resolution MFC achieves sensitivity levels equivalent to NGS . The IMWG response criteria state different response categories, depending on the method employed for MRD assessment Still, it makes more sense to establish the quality of response for MRD according to the depth of response, instead of the technique employed.…”

Section: Discussionmentioning

confidence: 99%

Imaging and bone marrow assessments improve minimal residual disease prediction in multiple myeloma

et al. 2019

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The value of minimal residual disease (MRD) status by bone marrow and imaging analysis as independent prognostic factors has been well established in multiple myeloma (MM). Nevertheless data about their potential complementarity for a more accurate assessment are limited. With this aim, we retrospectively analyzed the prediction of outcome with the combination of PET‐CT and MRD, assessed by multiparameter flow cytometry (MFC) in 103 patients with newly diagnosed MM. We confirmed the benefit in terms of progression‐free survival (PFS), linked to the achievement of negativity by MFC (hazard ratio [HR] 0.53; 95% confidence interval [CI]: 0.28‐0.98), and PET‐CT (HR 0.18; 95% CI: 0.09‐0.36) individually. By combining both techniques, patients who became MRD‐/PET‐, with a median of PFS 92 months, had significant prolonged median PFS (P < .001). This is compared with MRD+/PET‐ and PET+ patients (median PFS of 45 and 28 months, respectively). We observed a significant difference (P = .003) in overall survival (OS) outcomes between MRD‐/PET‐ and MRD+/PET‐ patients (4‐year OS 94.2% and 100%, respectively), vs PET+ patients (4‐year OS 73.8%). All survival results were confirmed in a conditional landmark analysis. These findings support the potential complementarity between PET‐CT and MFC, and highlight their better predictive capability when improving sensitivity.

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Section: Discussionmentioning

confidence: 99%

Imaging and bone marrow assessments improve minimal residual disease prediction in multiple myeloma

et al. 2019

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“…Flow cytometry in expert hands (available in a small number of expert centers) can reach sensitivities similar to NGS; however, there is still lack of standardization across laboratories. Loss of cells during antibody staining and use of more than one tube increases the number of cells required to guarantee 10 −6 sensitivity (3 million for the MSKCC 10‐color single tube assay and 10 million for the EuroFlow 8‐color two‐tube assay).…”

Section: Technological Advancesmentioning

confidence: 99%

Meeting report: Advances in minimal residual disease testing in multiple myeloma 2018

Landgren

Rustad

2018

Adv Cell Gene Ther

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This report summarizes the 5th annual symposium on minimal residual disease (MRD) testing in multiple myeloma gathered experts from academia, industry and the FDA in New York City on 14 September 2018. Three recommendations were made: (a) MRD testing should be performed in patients who achieve a very good partial response (VGPR) in addition to complete response (CR); (b) MRD negativity at one tumor cell in 1 000 000 bone marrow cells (10 −6 ) should be considered as a response category alongside the current definition of MRD negativity at 10 −5 ; and (c) clinical trials reports should specify the sensitivity of MRD testing as well as the applied threshold for MRD negativity (ie, 10 −5 or 10 −6 ), and if possible report outcome data for both MRD thresholds. Overall, as discussed at the meeting, there is already solid evidence that bone marrow based MRD assessment is one of the strongest prognostic factors in multiple myeloma, and deeper responses correlate with increasingly favorable outcomes. Indeed, achieving MRD negativity appears to be more important than what treatment was used to get there. Going forward, there is a need for clinical trials focusing on MRD-directed therapy to determine the role of MRD testing in everyday clinical decision-making. Standardization of MRD testing and harmonization across centers will make it easier to learn from common experiences.Ongoing efforts are anticipated to establish MRD status as a regulatory endpoint for accelerated drug approval in multiple myeloma in the near future.

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“…To address this concern, the EuroFlow™ consortium developed next‐generation flow (NGF), which consists of 2 standardized flow cytometry tubes with 8 antibodies each, analytical process, event acquisition and data analysis using proprietary software (Flores‐Montero et al ) (Table ). Recently, investigators from the Memorial Sloan Kettering Cancer Center (Roshal et al , ) developed a single tube, 10‐colour method with results comparable to EuroFlow™, although the EuroFlow™ method is able to run a higher number of cells and provides an intra‐assay confirmation with 2 tubes.…”

Section: Challengesmentioning

confidence: 99%

Challenges and opportunities in the assessment of measurable residual disease in multiple myeloma

et al. 2019

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Summary Treatment response assessment in multiple myeloma (MM) relies on the detection of paraprotein in serum and/or urine, bone marrow morphology and immunohistochemistry. With remarkable advances in therapy, particularly in the newly diagnosed setting, achievement of complete remission became frequent, creating the need to identify smaller amounts of residual disease and understand their prognostic and therapeutic implications. Measurable residual disease (MRD) can be assessed primarily by flow cytometry and next generation sequencing and state‐of‐the‐art assays have sensitivity approaching 1 in 106 cells. This review discusses the existing challenges in utilizing MRD to inform management of MM and highlights open research questions and opportunities as MRD is more routinely incorporated into clinical practice for patients with MM.

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MRD detection in multiple myeloma: comparison between MSKCC 10-color single-tube and EuroFlow 8-color 2-tube methods

Abstract: Key Points Methods that use an MSKCC single 10-color tube or EuroFlow two 8-color tubes provide similar sensitivity in the detection of MRD in multiple myeloma.

Cited by 91 publications

References 17 publications

Imaging and bone marrow assessments improve minimal residual disease prediction in multiple myeloma

Imaging and bone marrow assessments improve minimal residual disease prediction in multiple myeloma

Meeting report: Advances in minimal residual disease testing in multiple myeloma 2018

Challenges and opportunities in the assessment of measurable residual disease in multiple myeloma

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