MRD in multiple myeloma: does CR really matter?

Miguel, Jesús F. San; Avet-Loiseau, Hervé

doi:10.1182/blood.2022016170

Cited by 23 publications

(15 citation statements)

References 45 publications

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“…NGF, which relies on antibodies targeting cell surface proteins, and NGS, which identifies genetic mutations, focus on distinct biological markers [ 36 , 37 ]. This divergence in methodological focus can lead to scenarios where MRD is detectable by one technique but remains undetected by the other, reflecting the distinct detection capabilities inherent to each method [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of next-generation sequencing versus next-generation flow cytometry for minimal-residual-disease detection in Chinese patients with multiple myeloma

Zhou,

Chen,

Gong

et al. 2024

Discov Onc

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Purpose To evaluate the efficacy of next-generation sequencing (NGS) in minimal-residual-disease (MRD) monitoring in Chinese patients with multiple myeloma (MM). Methods This study analyzed 60 Chinese MM patients. During MRD monitoring in these patients’ post-therapy, clonal immunoglobulin heavy chain (IGH) rearrangements were detected via NGS using LymphoTrack assays. MRD monitoring was performed using NGS or next-generation flow cytometry (NGF), and the results were compared. Additionally, the sensitivity and reproducibility of the NGS method were assessed. Results The MRD detection range of the NGS method was 10–6–10–1, which suggested good linearity, with a Pearson correlation coefficient of 0.985 and a limit of detection of 10–6. Intra- and inter-assay reproducibility analyses showed that NGS exhibited 100% reproducibility with low variability in clonal cells. At diagnosis, unique clones were found in 42 patients (70.0%) with clonal IGH rearrangements, which were used as clonality markers for MRD monitoring post-therapy. Comparison of NGS and NGF for MRD monitoring showed 79.1% concordance. No samples that tested MRD-positive via NGF were found negative via NGS, indicating the higher sensitivity of NGS. MRD could be detected using NGS in 6 of 7 samples before autologous hematopoietic stem-cell transplantation, and 5 of them tested negative post-transplantation. In contrast, the NGF method could detect MRD in only 1 sample pre-transplantation. Conclusion Compared with NGF, NGS exhibits higher sensitivity and reproducibility in MRD detection and can be an effective strategy for MRD monitoring in Chinese MM patients.

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Section: Discussionmentioning

confidence: 99%

Evaluation of next-generation sequencing versus next-generation flow cytometry for minimal-residual-disease detection in Chinese patients with multiple myeloma

Zhou,

Chen,

Gong

et al. 2024

Discov Onc

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“…Clinical studies did not definitively clarify neither what the ideal threshold of sensitivity is, the optimal timing for MRD assessment, nor if achievement of MRD negativity has the same value in SR, HR or ultra-high-risk patients, given that the MASTER trial [ 130 ] showed different outcomes in these groups of patients despite MRD negativity. Moreover, the discordance between the achievement of CR according to IMWG criteria [ 120 ] and MRD negativity [ 241 ] should be better explained. Another unresolved issue is in regard to the minimal duration of sustained MRD negativity required to be a strong prognostic factor since, as reported in patients enrolled in the MAIA and ALCYONE trials [ 124 ], PFS was not the same when sustained MRD lasted less or more than 12 months.…”

Section: Discussion and Expert Opinionmentioning

confidence: 99%

Current Main Topics in Multiple Myeloma

Morè¹,

Corvatta²,

Manieri³

et al. 2023

Cancers

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Multiple Myeloma (MM) remains a difficult to treat disease mainly due to its biological heterogeneity, of which we are more and more knowledgeable thanks to the development of increasingly sensitive molecular methods that allow us to build better prognostication models. The biological diversity translates into a wide range of clinical outcomes from long-lasting remission in some patients to very early relapse in others. In NDMM transplant eligible (TE) patients, the incorporation of mAb as daratumumab in the induction regimens, followed by autologous stem cell transplantation (ASCT) and consolidation/maintenance therapy, has led to a significant improvement of PFS and OS.; however, this outcome remains poor in ultra-high risk MM or in those who did not achieve a minimal residual disease (MRD) negativity. Several trials are exploring cytogenetic risk-adapted and MRD-driven therapies in these patients. Similarly, quadruplets-containing daratumumab, particularly when administered as continuous therapies, have improved outcome of patients not eligible for autologous transplant (NTE). Patients who become refractory to conventional therapies have noticeably poor outcomes, making their treatment a difficult challenge in need of novel strategies. In this review, we will focus on the main points regarding risk stratification, treatment and monitoring of MM, highlighting the most recent evidence that could modify the management of this still incurable disease.

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“…It is now well established that bone marrow based MRD evaluation provides better prognostic performance than SPEP/IFE [56]. Intriguingly, there are reports indicating that among patients with MRD-negativity, achievement of complete response based on conventional IMWG criteria (i.e., negative by SPEP/IFE) does not affect prognosis [57], raising a concern about false-positive SPEP/IFE results. M-protein detection by mass spectrometry (MS) has a potential to address both aforementioned shortcomings of the classical method.…”

Section: Mass Spectrometrymentioning

confidence: 99%

Measurable residual disease in peripheral blood in myeloma: dream or reality

Kubicki,

Derman,

Dytfeld

et al. 2023

Current Opinion in Oncology

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Purpose of review Therapeutic advancements in multiple myeloma have led to increasingly deeper and more durable responses, creating a need for highly sensitive and applicable techniques for measurable residual disease (MRD) assessment. Bone marrow assays can deeply assess for MRD, but it is not conducive to performing frequent and dynamic evaluations, which may be needed for MRD-adapted treatment approaches. Recently, numerous techniques for MRD assessment in peripheral blood have come under investigation, and their integration into routine clinical practice is eagerly anticipated. Recent findings The identification of circulating tumor cells (CTCs), evaluation of cell-free DNA, and measuring monoclonal protein concentration with mass spectrometry are promising research areas for assessing myeloma in peripheral blood. CTCs assessment and cell-free DNA may carry prognostic significance, but they lack the sensitivity of bone marrow-based techniques. Mass spectrometry has already been implemented in clinical practice in certain centers, but its full potential has yet to be fully realized. This review focuses on recent developments in these fields, emphasizing the potential future roles of these assessments. Summary MRD assessment in peripheral blood is still in the development stage but holds promise for not only complementing bone marrow based evaluations but also potential for improving sensitivity.

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MRD in multiple myeloma: does CR really matter?

Cited by 23 publications

References 45 publications

Evaluation of next-generation sequencing versus next-generation flow cytometry for minimal-residual-disease detection in Chinese patients with multiple myeloma

Evaluation of next-generation sequencing versus next-generation flow cytometry for minimal-residual-disease detection in Chinese patients with multiple myeloma

Current Main Topics in Multiple Myeloma

Measurable residual disease in peripheral blood in myeloma: dream or reality

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