Next-generation sequencing-based monitoring of circulating tumor DNA reveals clonotypic heterogeneity in untreated PTCL.
Milos D MiljkovicChristopher MelaniStefania PittalugaRahul LakhotiaNicole LucasAllison JacobErik YuskoElaine S JaffeWyndham H WilsonMark J RoschewskiPublished in: Blood advances (2021)
Peripheral T-cell lymphomas (PTCLs) have marked biologic and clinical heterogeneity, which confounds treatment decisions. Advances in circulating tumor DNA (ctDNA) assays using next-generation sequencing (NGS) have improved the detection of molecular relapse and driver mutations in diffuse large B-cell lymphoma and show the potential utility of ctDNA across lymphomas. We investigated NGS-based monitoring of T-cell receptor (TCR) sequences in patients with PTCL undergoing frontline treatment. Of 45 patients, 34 (76%) had tumor-specific clonotypes of the TCRβ or TCRγ genes identified, which included 18 (86%) from baseline tissue and 16 (67%) from baseline serum. Twenty-five (74%) patients had both TCRβ and TCRγ clonotypes, 23 (68%) had more than 1 TCRγ clonotype, and 4 (9%) had multiple TCRβ or TCRγ clonotypes, demonstrating significant intrapatient clonotypic heterogeneity. Among 24 patients with available serial serum samples during treatment, 9 (38%) cleared ctDNA after 2 cycles of therapy, and 11 (46%) had detectable ctDNA at the end of treatment. Patients with detectable ctDNA after therapy showed a trend toward worse survival. Notably, 2 patients with persistently detectable ctDNA after therapy remained in remission with 10 years of follow-up. Clonotypic heterogeneity in tumors and persistence, despite long-term remission, suggests variability in oncological potential. This trial was registered at www.clinicaltrials.gov as #NCT00001337.
Keyphrases
- circulating tumor
- regulatory t cells
- cell free
- circulating tumor cells
- diffuse large b cell lymphoma
- single cell
- dendritic cells
- ejection fraction
- clinical trial
- stem cells
- end stage renal disease
- epstein barr virus
- prostate cancer
- disease activity
- single molecule
- bone marrow
- gene expression
- systemic lupus erythematosus
- cell therapy
- mass spectrometry
- genome wide
- dna methylation
- phase iii
- mesenchymal stem cells
- quantum dots
- real time pcr