Ig Gene Clonality Analysis Using Next-Generation Sequencing for Improved Minimal Residual Disease Detection with Significant Prognostic Value in Multiple Myeloma Patients

Abstract

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Real‐world data on prognostic value of measurable residual disease assessment by fragment analysis or next‐generation sequencing in multiple myeloma

“…The proportion of patients who received a triplet induction regimen was lower in the fragment analysis cohort compared with those in the NGS cohort, owing to the reimbursement issues in the earlier period, but recent work has proved the PFS surrogacy of MRD negativity regardless of induction regimens, 28 suggesting the minor role of the induction regimen in our analysis. We have also lately shown that the detection rate of clonality was similar between fragment analysis and NGS in diagnostic BM aspirates of patients with MM (96.7% and 95.4% respectively) 22 . However, fragment analysis has a sensitivity of 10 −2 , as it identifies clonality based on the PCR product size, rather than the difference in sequence, limiting its value as a tool for MRD monitoring.…”

“…We have also lately shown that the detection rate of clonality was similar between fragment analysis and NGS in diagnostic BM aspirates of patients with MM (96.7% and 95.4% respectively). 22 However, fragment analysis has a sensitivity of 10 −2 , as it identifies clonality based on the PCR product size, rather than the difference in sequence, limiting its value as a tool for MRD monitoring. Of note, fragment analysis has never been tested as a tool for MRD modality for predicting survival in MM, and our data reveal that fragment analysis should not be recommended for MRD detection or monitoring in MM.…”

“…This assay ditinguishes clonality from the standpoint of PCR product size, where fluorescence‐tagged PCR fragments are analysed using a capillary electrophoresis sequencer following PCR involving multiplex primers established by the EuroClonality/BIOMED‐2 consortium 23 . Although the sensitivity of fragment analysis is low (10 −2 ), this analysis is simple and rapid with an affordable price 22 . However, the potential of fragment analysis as an MRD test has not been evaluated in patients with MM.…”

“…Prior to the advent of NGS technology, our group examined the clonality of the IGH and IGK genes by fragment analysis with the commercially available IdentiClone® (Invivoscribe) kit for MRD assessment in real-world patients with MM. 22 This assay ditinguishes clonality from the standpoint of PCR product size, where fluorescence-tagged PCR fragments are analysed using a capillary electrophoresis sequencer following PCR involving multiplex primers established by the EuroClonality/BIOMED-2 consortium. 23 Although the sensitivity of fragment analysis is low (10 −2 ), this analysis is simple and rapid with an affordable price.…”

“…23 Although the sensitivity of fragment analysis is low (10 −2 ), this analysis is simple and rapid with an affordable price. 22 However, the potential of fragment analysis as an MRD test has not been evaluated in patients with MM.…”