Peripheral T-cell lymphomas (PTCLs) represent a highly heterogeneous class of lymphomas with variable responses to treatments. A team of researchers conducted a study to identify features related to heterogeneity in PTCLs that may be associated with treatment outcomes, and they reported their results in the journal Blood Advances.
This study (ClinicalTrials.gov Identifier: NCT00001337) included patients with PTCL who were given dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH) as frontline treatment. Diagnostic biopsy specimens and/or serum samples were obtained, and serum was also collected prior to each cycle of chemotherapy, on completion of induction, and during surveillance appointments. Next-generation sequencing of T-cell receptor (TCR) gene sequences was performed on biopsy specimens and circulating tumor DNA (ctDNA) in the serum. The researchers investigated TCR-related sequence patterns in terms of treatment responses.
A total of 45 patients had baseline biopsy and/or serum samples for use in monitoring tumor-specific clonotypes, of whom 34 patients (76%) demonstrated a tumor-specific clonotype in baseline tissue and/or serum, and these patients formed the study cohort. Patients had a median of 3 (range, 1-8) dominant TCR clonotypes found within biopsy and/or serum samples. A total of 18 patients had a dominant TCR clonotype in a biopsy sample, of whom 17 showed dominant clonotypes for both TCRb and TCRg genes in these samples. Throughout the study cohort, the researchers found a total of 63 dominant TCR clonotypes, with variation in numbers of dominant TCR clonotypes found among PTCL subtypes.
Subtypes of PTCL showed differences in survival outcomes at a median follow-up of 3.0 years (range, 0.1-15.4). Anaplastic large cell lymphoma (ALCL) was associated with the longest event-free survival (EFS), with a median of 15.1 years, compared with 0.65 years for other PTCL subtypes (P =.01). However, ALCL showed no difference in overall survival (OS) vs other PTCL subtypes. Patients who had high vs low levels of baseline ctDNA did not demonstrate a significant difference in EFS or in OS.
Serial serum samples were available for 24 patients over the course of therapy, with 63% of these patients showing persistent ctDNA following 2 cycles of therapy, and detectable ctDNA remaining in 46% of patients upon completion of treatment. Presence of ctDNA after treatment completion was linked to nonsignificant trends of poorer EFS and OS.
Regarding the use of ctDNA for surveillance after therapy, in cases of clinical relapse, changes in ctDNA patterns varied across patients. For instance, 1 patient showed a gradual increase in ctDNA during the months before clinical progression was evident, while another patient had varied ctDNA levels throughout the surveillance period prior to showing clinical progression 8 years following treatment.
“In summary, high-throughput sequencing of the TCR detected dominant and likely tumor-specific clonotypes in most of the patients with PTCL and successfully tracked those clonotypes throughout therapy,” the researchers concluded in their report.
Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Miljkovic MD, Melani C, Pittaluga S, et al. Next-generation sequencing–based monitoring of circulating tumor DNA reveals clonotypic heterogeneity in untreated PTCL. Blood Adv. 2021;5(20):4198-4210. doi:10.1182/bloodadvances.2020003679