101. Baseline identification of clonal V(D)J sequences for DNA-based minimal residual disease detection in multiple myeloma.
- Author
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Rustad EH, Hultcrantz M, Yellapantula VD, Akhlaghi T, Ho C, Arcila ME, Roshal M, Patel A, Chen D, Devlin SM, Jacobsen A, Huang Y, Miller JE, Papaemmanuil E, and Landgren O
- Subjects
- Aged, Bone Marrow Cells metabolism, Female, Humans, Immunoglobulin Heavy Chains genetics, Immunoglobulin kappa-Chains genetics, Male, Middle Aged, Sequence Analysis, DNA, Multiple Myeloma diagnosis, Multiple Myeloma genetics, Neoplasm, Residual diagnosis, Neoplasm, Residual genetics, V(D)J Recombination
- Abstract
Tracking of clonal immunoglobulin V(D)J rearrangement sequences by next generation sequencing is highly sensitive for minimal residual disease in multiple myeloma. However, previous studies have found variable rates of V(D)J sequence identification at baseline, which could limit tracking. Here, we aimed to define the factors influencing the identification of clonal V(D)J sequences. Bone marrow mononuclear cells from 177 myeloma patients underwent V(D)J sequencing by the LymphoTrack assays (Invivoscribe). As a molecular control for tumor cell content, we sequenced the samples using our in-house myeloma panel myTYPE. V(D)J sequence clonality was identified in 81% of samples overall, as compared with 95% in samples where tumor-derived DNA was detectable by myTYPE. Clonality was detected more frequently in patients with lambda-restricted disease, mainly because of increased detection of kappa gene rearrangements. Finally, we describe how the tumor cell content of bone marrow aspirates decrease gradually in sequential pulls because of hemodilution: From the initial pull used for aspirate smear, to the final pull that is commonly used for research. In conclusion, baseline clonality detection rates of 95% or higher are feasible in multiple myeloma. Optimal performance depends on the use of good quality aspirates and/or subsequent tumor cell enrichment., Competing Interests: We have all read the journal's policy and the authors of this manuscript have the following competing interests: YH, AJ and JEM are employees and shareholders of Invivoscribe, Inc. CH has received Honorarium from Invivoscribe, Inc. OL has grant support from: NIH, FDA, MMRF, IMF, LLS, Perelman Family Foundation, Rising Tides Foundation, Amgen, Celgene, Janssen, Takeda, Glenmark, Seattle Genetics, Karyopharm; has received Honoraria/participated in ad boards by: Adaptive, Amgen, Binding Site, BMS, Celgene, Cellectis, Glenmark, Janssen, Juno, Pfizer; and served on the Independent Data Monitoring Committees (IDMC) for: Takeda, Merck, Janssen. Neither of the above alters our adherence to PLOS ONE policies on sharing data and materials. The remaining authors declare no relevant conflicts of interest.
- Published
- 2019
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