Dataset Information

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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Publications

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:BackgroundMinimal residual disease (MRD) testing is a promising approach to tailor the treatment of multiple myeloma (MM). However, several major concerns remain to be addressed before moving it into daily practice, most of which stem from the dynamic nature of the MRD status. Thus, it is crucial to understand the MRD dynamics and propose its clinical implications.MethodsWe retrospectively analysed the data of patients with newly diagnosed MM (NDMM) who had flow cytometry-based MRD tests at multiple time points after initiation of therapy. The impact of undetectable MRD (including attainment, duration and loss) on clinical outcomes was analysed.ResultsIn a cohort of 220 patients with NDMM, attainment of MRD- offered favourable outcomes (P < 0.0001 for both progression-free survival (PFS) and overall survival (OS)), regardless of baseline risk factors. Notably, MRD- duration ≥12 months was associated with an 83 % (95 % confidence interval (CI), 0.09-0.34; P < 0.0001) or 69 % (95 % CI, 0.13-0.76; P = 0.0098) reduction in risk of progression/death or death, while the longer MRD- was sustained, the better the outcome was. Loss of MRD- led to poor PFS (hazard ratio (HR) 0.01, 95 % CI 0-0.06, P < 0.0001) and OS (HR 0.03, 95 % CI 0-0.24, P = 0.0008). Most patients (70 %) who lost MRD- status carried high-risk cytogenetic abnormalities (HRCAs). While MRD- was temporally inconsistent with conventional therapeutic responses (eg ≥ complete remission or very good partial response), it predicted disease progression or recurrence more robustly than the latter. Last, the predictive value of the MRD status was independent of baseline risk factors (eg high-risk cytogenetic abnormality, International Staging System (ISS) or Revised (R-)ISS staging).ConclusionsLongitudinal assessment of MRD during the treatment course and follow-up is required for monitoring disease progression or relapse, to guide treatment decisions. Accordingly, a prospective study is currently ongoing to investigate the feasibility and benefit of the MRD-tailored therapy according to the longitudinal changes of the MRD status.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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