T-cell receptor repertoire analysis by next-generation sequencing peripheral blood mononuclear cells from multiple myeloma or smoldering multiple myeloma patients

Multiple myeloma (MM) is a hematological malignancy mostly assessed by bone marrow involvement, so it is attractive to develop a method using peripheral blood. We hypothesized that peripheral blood mononuclear cells (PBMCs) may replace tedious and invasive bone marrow biopsies as a biomarker. In this study, we aimed to investigate if T-cell receptor (TCR) repertoire has clinical significance in MM or Smoldering MM (SMM) diagnosis or prognosis. Using baseline genomic DNA (PBMC) from 24 patients with SMM and 31 patients with MM, we performed next-generation sequencing on the Illumina NextSeq 500 platform by immunoSEQ TCRB Kits from Adaptive Biotechnology to quantitatively assay the complementarity determining region 3 (CDR3) of human T-cell receptor β (TCRβ) gene. To evaluate T-cell diversity and clonality, we performed pipeline analysis by ImmunoAnalyzer from Adaptive Technology, and downloaded sequencing data with manual analysis by JMP13 software. Compared to TCRB data from 280 normal control (Age > 40) PBMCs (Nat Genet. 2017, 49(5):659-665), we found less TCR templates from both MM and SMM baseline based on size of TCRB repertoire, and less TCR rearrangements or unique clonotypes based on structure of TCRB repertoires. Only MM baseline showed higher maximum clonotype frequency. No difference of T-cell clonality was found from MM and SMM. Furthermore, we performed the same sequencing on 18 SMM patients at different treatment time points including chemotherapy after cycle 8, 20, and 32. Our results showed patient samples after cycle 8 had less TCR templates and TCR rearrangements compared to those from the other three time points although no significant difference were found in maximum clonotype frequency or T-cell clonality. TCR overlap analysis will be further performed to track potential clonotype changes. Thus, we identified TCR repertoire analysis may have potential clinical significance as biomarker assay for MM and SMM patients. Citation Format: Yong Zhang, Svetlana Petrovskaya, Emma C. Scott, Luis Santana-Quintero, Tigran Ghazanchyan, Amy Rosenburg, V. Ashutosh Rao, Gideon M. Blumenthal, Marc Theoret, Richard Pazdur, Julia A. Beaver, Dickran Kazandjian. T-cell receptor repertoire analysis by next-generation sequencing peripheral blood mononuclear cells from multiple myeloma or smoldering multiple myeloma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 5141.