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The clinical significance of stringent complete response in multiple myeloma is surpassed by minimal residual disease measurements.

ABSTRACT: BACKGROUND:Stringent complete response (sCR) is used as a deeper response category than complete response (CR) in multiple myeloma (MM) but may be of limited value in the era of minimal residual disease (MRD) testing. METHODS:Here, we used 4-colour multiparametric flow cytometry (MFC) or next-generation sequencing (NGS) of immunoglobulin genes to analyse and compare the prognostic impact of sCR and MRD monitoring. We included 193 treated patients in two institutions achieving CR, for which both bone marrow aspirates and biopsies were available. RESULTS:We found that neither the serum free light chain ratio, clonality by immunohistochemistry (IHC) nor plasma cell bone marrow infiltration identified CR patients at distinct risk. Patients with sCR had slightly longer progression-free survival. Nevertheless, persistent clonal bone marrow disease was detectable using MFC or NGS and was associated with significantly inferior outcomes compared with MRD-negative cases. CONCLUSION:Our results confirm that sCR does not predict a different outcome and indicate that more sensitive techniques are able to identify patients with differing prognoses. We suggest that MRD categories should be implemented over sCR for the future classification of MM responses.

SUBMITTER: Cedena MT

PROVIDER: S-EPMC7458342 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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The clinical significance of stringent complete response in multiple myeloma is surpassed by minimal residual disease measurements.

Cedena Maria-Teresa MT Martin-Clavero Estela E Wong Sandy S Shah Nina N Bahri Natasha N Alonso Rafael R Barcenas Carmen C Valeri Antonio A Salazar Tabares Johny J Sanchez-Pina Jose J Cuellar Clara C Martin Thomas T Wolf Jeffrey J Lahuerta Juan-Jose JJ Martinez-Lopez Joaquin J

PloS one 20200831 8

<h4>Background</h4>Stringent complete response (sCR) is used as a deeper response category than complete response (CR) in multiple myeloma (MM) but may be of limited value in the era of minimal residual disease (MRD) testing.<h4>Methods</h4>Here, we used 4-colour multiparametric flow cytometry (MFC) or next-generation sequencing (NGS) of immunoglobulin genes to analyse and compare the prognostic impact of sCR and MRD monitoring. We included 193 treated patients in two institutions achieving CR, ...[more]

PMID: 32866200

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Project description:Assessment of minimal residual disease (MRD) is becoming a standard diagnostic tool for curable hematological malignancies such as chronic and acute myeloid leukemia. Multiple myeloma (MM) remains an incurable disease, as a major portion of patients even in complete response eventually relapse, suggesting that residual disease remains. Over the past decade, the treatment landscape of MM has radically changed with the introduction of new effective drugs and the availability of immunotherapy, including targeted antibodies and adoptive cell therapy. Therefore, conventional serological and morphological techniques have become suboptimal for the evaluation of depth of response. Recently, the International Myeloma Working Group (IMWG) introduced the definition of MRD negativity as the absence of clonal Plasma cells (PC) with a minimum sensitivity of <10-5 either by next-generation sequencing (NGS) using the LymphoSIGHT platform (Sequenta/Adaptative) or by next-generation flow cytometry (NGF) using EuroFlow approaches as the reference methods. While the definition of the LymphoSIGHT platform (Sequenta/Adaptive) as the standard method derives from its large use and validation in clinical studies on the prognostic value of NGS-based MRD, other commercially available options exist. Recently, the LymphoTrack assay has been evaluated in MM, demonstrating a sensitivity level of 10-5, hence qualifying as an alternative effective tool for MRD monitoring in MM. Here, we will review state-of-the-art methods for MRD assessment by NGS. We will summarize how MRD testing supports clinical trials as a useful tool in dynamic risk-adapted therapy. Finally, we will also discuss future promise and challenges of NGS-based MRD determination for clinical decision-making. In addition, we will present our real-life single-center experience with the commercially available NGS strategy LymphoTrack-MiSeq. Even with the limitation of a limited number of patients, our results confirm the LymphoTrack-MiSeq platform as a cost-effective, readily available, and standardized workflow with a sensitivity of 10-5. Our real-life data also confirm that achieving MRD negativity is an important prognostic factor in MM.

Dataset Information

The clinical significance of stringent complete response in multiple myeloma is surpassed by minimal residual disease measurements.

Publications

The clinical significance of stringent complete response in multiple myeloma is surpassed by minimal residual disease measurements.

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