Synapse - Capture rate of V(D)J sequencing for minimal residual disease detection in multiple myeloma

Capture rate of V(D)J sequencing for minimal residual disease detection in multiple myeloma Journal Article

Authors:	Hultcrantz, M.; Rustad, E. H.; Yellapantula, V.; Jacob, A.; Akhlaghi, T.; Korde, N.; Mailankody, S.; Lesokhin, A. M.; Hassoun, H.; Smith, E. L.; Lahoud, O. B.; Landau, H. J.; Shah, G. L.; Scordo, M.; Chung, D. J.; Giralt, S.; Papaemmanuil, E.; Landgren, O.
Article Title:	Capture rate of V(D)J sequencing for minimal residual disease detection in multiple myeloma
Abstract:	PURPOSE: Minimal residual disease (MRD) negativity is a strong predictor for outcome in multiple myeloma. To assess V(D)J clonotype capture using the updated Adaptive next-generation sequencing (NGS) MRD assay in a clinical setting, we analyzed baseline and follow-up samples from patients with multiple myeloma who achieved deep clinical responses. EXPERIMENTAL DESIGN: A total of 159 baseline and 31 follow-up samples from patients with multiple myeloma were sequenced using the NGS MRD assay. Baseline samples were also sequenced using a targeted multiple myeloma panel (myTYPE). We estimated ORs with 95% confidence intervals (CI) for clonotypes detection using logistic regression. RESULTS: The V(D)J clonotype capture rate was 93% in baseline samples with detectable genomic aberrations, indicating presence of tumor DNA, assessed through myTYPE. myTYPE-positive samples had significantly higher V(D)J clonotype detection rates in univariate (OR, 7.3; 95% CI, 2.8-22.6) and multivariate analysis (OR, 4.4; 95% CI, 1.4-16.9; P = 0.016). Higher disease burden was associated with higher probability of V(D)J clonotype capture, meanwhile no such association was found for age, gender, or type of heavy or light immunoglobulin chain. All V(D)J clonotypes detected at baseline were detected in MRD-positive samples indicating that the V(D)J clonotypes remained stable and did not undergo further rearrangements during follow-up. Of the 31 posttreatment samples, 12 were MRD-negative using the NGS MRD assay. CONCLUSIONS: NGS for V(D)J rearrangements in multiple myeloma offers a reliable and sensitive method for MRD tracking with high detection rates in the clinical setting. ©2022 American Association for Cancer Research.
Keywords:	genetics; multiple myeloma; dna; gene rearrangement; minimal residual disease; neoplasm, residual; dna, neoplasm; procedures; high throughput sequencing; high-throughput nucleotide sequencing; humans; human
Journal Title:	Clinical Cancer Research
Volume:	28
Issue:	10
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2022-05-15
Start Page:	2160
End Page:	2166
Language:	English
DOI:	10.1158/1078-0432.Ccr-20-2995
PUBMED:	35553646
PROVIDER:	scopus
PMCID:	PMC9179004
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85130051535&doi=10.1158%2f1078-0432.CCR-20-2995&partnerID=40&md5=537dbdb82de1bbf249f22072b1cde466
Notes:	Article -- Export Date: 1 June 2022 -- Source: Scopus