Relevance of polyclonal plasma cells and post-therapy immunomodulation in measurable residual disease assessment in multiple myeloma
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Updated: Sep 27, 2025
An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Nupur Das1, Meetu Dahiya1, Ritu Gupta1
1Laboratory Oncology Unit, Dr. B.R. Ambedkar IRCH, All India Institute of Medical Sciences, New Delhi, India.
Background:
Immunophenotypic profile and post-therapy alteration in antigenic expression were evaluated in normal, reactive, and aberrant plasma cells (NPC, RPC, and APC) for impact on measurable residual disease (MRD) assessment in multiple myeloma (MM).
Methods:
Samples from non-MM staging marrow (n = 30), Hodgkin's lymphoma (n = 30) and MM (n = 724) were prospectively evaluated for expression profiles of NPC, RPC, and APC using antigens recommended in consensus guidelines.
Results:
Polyclonal NPC-RPC demonstrated aberrations for all antigens evaluated with a higher frequency of aberrancies in post-therapy samples compared to treatment naïve samples (p < 0.001%). Immunomodulation in APC was observed in 79% of post-therapy samples with a change in expression of 1, 2, and ≥3 antigens in 19.9%, 15.6%, and 43.5% samples, respectively. In 13.4% of samples, APC showed no aberrancy and aberrant status was assigned based on cytoplasmic light chain restriction (cyLCR) alone. 9% samples with an admixture of NPC and APC displayed normal cytoplasmic kappa to lambda ratio (cyKLR) when the percentage of APC of total PC (neoplastic plasma cell index, NPCI), was below 25% and 50% for kappa and lambda restricted cases, respectively.
Conclusion:
The panorama and high frequency of antigenic aberrations on polyclonal PC signify the importance of MRD assay validation on a large cohort under normal and reactive conditions. Frequent Immunophenotypic shifts in APC re-confirm the redundancy of baseline immunophenotype for MRD evaluation. Small clones of APC may be missed by assessment of cyKLR alone and therefore, surface marker aberrancy supported by cyLCR is required for definitive assignment of residual APC.
Insights
Assessing antigenic expression in normal, reactive, and aberrant plasma cells is crucial for accurate multiple myeloma measurable residual disease (MRD) detection. Post-therapy, frequent immunophenotypic shifts highlight the need for robust MRD assay validation.
Area of Science:
- Hematology
- Immunology
- Oncology
Background:
- Measurable residual disease (MRD) assessment in multiple myeloma (MM) relies on accurate immunophenotyping of plasma cells.
- Understanding antigenic expression in normal, reactive, and aberrant plasma cells (NPC, RPC, APC) is vital for reliable MRD detection.
Purpose of the Study:
- To evaluate the immunophenotypic profile and post-therapy alterations in antigenic expression of NPC, RPC, and APC.
- To determine the impact of these alterations on MRD assessment in MM.
Main Methods:
- Prospective evaluation of plasma cell antigens in non-MM marrow, Hodgkin's lymphoma, and MM samples.
- Utilized antigens recommended by consensus guidelines for NPC, RPC, and APC expression profiling.
Main Results:
- Polyclonal NPC-RPC showed frequent antigen aberrations, especially in post-therapy samples.
- Aberrant plasma cells (APC) exhibited significant immunomodulation post-therapy, with altered expression of multiple antigens.
- Cytoplasmic light chain restriction (cyLCR) alone was insufficient for APC identification in some cases.
Conclusions:
- High frequency of antigenic aberrations in polyclonal plasma cells necessitates MRD assay validation in normal and reactive conditions.
- Frequent immunophenotypic shifts in APC confirm the limitations of baseline immunophenotype for MRD evaluation.
- Accurate MRD assessment requires surface marker aberrancy combined with cyLCR for definitive APC identification.
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