Overview
Diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) are aggressive lymphomas commonly treated with first-line immunochemotherapy. Some patients experience disease progression or relapse despite treatment. PET/CT is used to assess treatment response, but it may not identify small amounts of residual lymphoma.
Circulating tumor DNA (ctDNA) consists of tumor-derived DNA fragments detectable in blood. This prospective observational study will use PhasED-seq to assess plasma ctDNA before, during, and after first-line therapy in approximately 100 patients with newly diagnosed DLBCL or HGBL.
The primary objective is to evaluate the association between ctDNA status approximately 8 weeks after completion of first-line therapy and subsequent progression-free survival. Additional analyses will examine overall survival, earlier ctDNA findings, and baseline tumor molecular subtypes. PET/CT findings will provide complementary information for exploratory analyses. The findings may inform future studies of response-adapted treatment.
Description
This is a multicenter, prospective, observational cohort study evaluating the prognostic value of circulating tumor DNA (ctDNA), measured using PhasED-seq, in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL). Approximately 100 patients will be enrolled. The primary objective is to assess the association between post-treatment ctDNA status and subsequent progression-free survival (PFS).
Patients will undergo baseline PET/CT imaging and tumor tissue next-generation sequencing (NGS). First-line immunochemotherapy will be selected and managed by the treating physician according to routine clinical practice and will not be assigned by the study. Interim PET/CT assessment is planned after 3 cycles of treatment, and post-treatment PET/CT is planned approximately 8 weeks after completion of first-line therapy. Plasma samples for PhasED-seq ctDNA analysis will be collected before initiation of first-line therapy, after 3 cycles of treatment, and approximately 8 weeks after completion of first-line therapy, within the protocol-specified sampling windows.
The primary analysis will include patients who are alive and progression-free at the protocol-specified post-treatment ctDNA blood draw and have an evaluable ctDNA result. Patients will be classified as ctDNA-positive or ctDNA-negative according to the result from this blood draw. PFS will be measured from this blood draw to the first documented disease progression or death from any cause, whichever occurs first, with a primary observation period of 18 months.
Additional analyses will evaluate overall survival and the associations of interim ctDNA status, baseline ctDNA status, and baseline tumor molecular subtype with post-treatment PFS. These analyses will use the primary analysis population, restricted as necessary to patients with evaluable results for the marker being investigated. Associations involving earlier biomarkers will therefore describe subsequent outcomes among patients who remain alive and progression-free at the post-treatment assessment. PET/CT findings will be examined alongside ctDNA findings in exploratory analyses.
Patients who discontinue or change first-line treatment will remain in the enrolled cohort. Subsequent treatment and clinical outcomes will continue to be recorded where consent permits. Inclusion in each analysis population and the handling of missing or unevaluable results will follow prespecified criteria in the study protocol and statistical analysis plan. An unevaluable ctDNA result will not be classified as ctDNA-negative.
Eligibility
Inclusion Criteria:
- Age ≥18 years, either sex.
- Histopathologically confirmed diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL).
- Planned to receive standard immunochemotherapy including at least CD20 monoclonal antibody and anthracycline, such as Pola-RCHP, R-CHOP, or R-DA-EPOCH.
- No maintenance therapy planned after completion of first-line treatment.
- Written informed consent obtained.
Exclusion Criteria:
- DLBCL/HGBL transformed from indolent B-cell lymphoproliferative disorders.
- HIV-positive large B-cell lymphoma.
- Prior chemotherapy, targeted therapy, or immunotherapy for large B-cell lymphoma.
- Investigator-assessed ineligibility for this study.
- Concomitant other malignancies.
