Plasma Cell Dyscrasias

MRD assessment

Last update: October 1st, 2019

The level of minimal residual disease (MRD) is paramount to link the depth of response and long-term outcome. Some patients that reach complete response (CR) have inferior progression free survival (PFS) which is due to positive minimal residual disease which will sooner or later provoke a relapse. The recent advances in treatment demand a more sensitive response criteria which includes minimal residual disease evaluation.

MRD has been defined as one of the best surrogate markers to predict overall survival (OS) and accelerate the approval of new therapies. The European Medicines Agency (EMA) and FDA have published guideline drafts to use MRD as clinical endpoint in multiple myeloma studies.

International Myeloma Working Group Response Criteria

The international myeloma working group has defined criteria for MRD evaluation and time points for its sustained negativity.

Sustained MRD-negative

MRD negativity in the marrow (NGF or NGS, or both) and by imaging as defined below, confirmed minimum of 1 year apart. Subsequent evaluations can be used to further specify the duration of negativity (e.g. MRD-negative at 5 years)

Flow MRD-negative

Absence of phenotypically aberrant clonal plasma cells by NGF on bone marrow aspirates using the EuroFlow™ standard operation procedure for MRD detection in multiple myeloma.

Sequencing MRD-negative

Absence of clonal plasma cells by NGS on bone marrow aspirate in which presence of a clone is defined as less than two identical sequencing reads obtained after DNA sequencing of bone marrow aspirates.

Imaging-positive MRD-negative

MRD negativity as defined by NGF or NGS plus disappearance of every area of increased tracer uptake found at baseline or a preceding PET/CT or decrease to less mediastinal blood pool SUV or decrease to less than that of surrounding normal tissue

Note: For MRD assessment, the first bone marrow aspirate should be sent to MRD (not for morphology) and this sample should be taken in one draw with a volume of minimally 2 mL (to obtain sufficient cells), but maximally 4–5 mL to avoid haemodilution.

Next Generation Flow™

In recent years, EuroFlow™ scientific consortium has developed a solution called Next Generation Flow in order to create and standardize fast, accurate and sensitive flow cytometry tests. Based on that knowledge, Cytognos offers a complete and scientific-based solution to cover all the needs for evaluation of plasma cell dyscrasias.

Following NGF methodology, Cytognos offers the MM MRD kit for patient monitoring after therapy with increased sensitivity due to a BulkLysis™ step. The two-tube approach is especially relevant to obtain replicant consistency.

In order to analyze the obtained impressive and complex amount of data Cytognos offers the software Infinicyt™. Moreover, to standardize the analysis, Infinicyt™ 2.0 includes reference databases developed by EuroFlow™, including the MM MRD database for monitoring of patients after treatment.

For sample acquisition, Cytognos provides the CE-IVD Omnicyt™ cytometer, which features are compatible with NGF and make it the perfect complement to our solution (EuroFlow™ and Cytognos) for plasma cell dyscrasias evaluation.

Resources

Bone Marrow tests

Multiple myeloma diagnosis

Tests to Find Multiple Myeloma

Publications:

  1. Arroz M, et al. Consensus guidelines on plasma cell myeloma minimal residual disease analysis and reporting. Cytometry B Clin Cytom. 2016 Jan;90(1):31-9. Go to publication
  2. Soh KT, Tario JD Jr, Wallace PK. Diagnosis of Plasma Cell Dyscrasias and Monitoring of Minimal Residual Disease by Multiparametric Flow Cytometry. Clin Lab Med. 2017 Dec;37(4):821–853. Go to publication
  3. Flores-Montero J, et al. Immunophenotype of normal vs. myeloma plasma cells: Toward antibody panel specifications for MRD detection in multiple myeloma. Cytometry B Clin Cytom. 2016 Jan;90(1):61-72. Go to publication
  4. Flores-Montero J, et al. Next Generation Flow for highly sensitive and standardized detection of minimal residual disease in multiple myeloma. Leukemia. 2017 Oct;31(10):2094-103. Go to publication
  5. Kumar S, et al. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016 Aug;17(8):e328-46. Go to publication