According to the results of a study published in Annals of Hematology, 2 novel analytical approaches for detecting malignant plasma cell clones appear to accurately indicate the course of multiple myeloma (MM) and may be valuable for monitoring patients with serologically nontrackable disease.

The researchers used next generation sequencing (NGS) of IGK and IGL variable (VJ) light chain rearrangements in cell-free DNA and multiparameter flow cytometry (MFC) of magnetically-enriched CD138-positive circulating plasma cells (me-MFC) to investigate disease burden in the peripheral blood (pB) of 80 unselected patients with MM treated at the Department of Hematology, Oncology and Immunology, Philipps-University Marburg, Germany.

Patients with MM were included in the study irrespective of state of disease and previous therapies, and disease or response state was assessed according to the International Myeloma Working Group guidelines. There was no fixed schedule for cell-free DNA or circulating plasma cell sample collection.

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From the 80 patients, 114 of 130 (87.7%) cell-free DNA samples were successfully sequenced and 196 of 205 me-MFC results were evaluable. The investigators detected MM clones in 38.9% of samples taken at initial diagnosis or relapse and in 11.8% of samples taken during complete remission (CR). They also found circulating MM plasma cells in 83.3% of initial diagnosis or relapse samples and 9.9% of CR samples.

In samples collected from patients with very good partial remission or CR, the residual disease assessment by NGS and me-MFC was 80% concordant. The investigators also found that 4 of 4 NGS and 5 of 8 me-MFC positive CR samples were from patients with oligo- or non-secretory myeloma. Time to progression trended toward a shorter duration when the investigators found evidence of residual myeloma in the pB (NGS negative vs NGS positive, P =.1487; me-MFC negative vs me-MFC positive, P =.0826).

“Taken together, our preliminary validation studies of two technical modifications of molecular and cell-based assays for detecting MM in the pB support a future perspective to develop gradual follow-up concepts for MM patients that schedule investigations of BM samples only when there is no evidence of disease in the pB,” concluded the authors.

The investigators highlighted the need for further studies in larger patient cohorts to directly compare NGS- and MFC-approaches for monitoring of MM.


Mack EKM, Hartmann S, Ross P, et al. Monitoring multiple myeloma in the peripheral blood based on cell-free DNA and circulating plasma cells. Published online February 1, 2022. Ann Hematol. doi:10.1007/s00277-022-04771-5