Tumor-informed ctDNA assessment as a valuable prognostic and predictive biomarker in diffuse large B-cell lymphoma.

Background

A novel approach for molecular residual disease (MRD) detection and treatment monitoring is needed in diffuse large B-cell lymphoma (DLBCL) to identify patients with a poor prognosis. We performed a retrospective evaluation of commercial ctDNA testing in patients with stage I-IV DLBCL to evaluate the prognostic and predictive role of tumor-informed ctDNA assessment.

Methods

A personalized and tumor-informed multiplex PCR assay (Signatera™ bespoke mPCR NGS assay) was used for ctDNA detection and quantification.

Results

In total, 50 patients (median age: 59 years; median follow-up: 12.68 months) were analyzed, of which 41 had pretreatment time points with ctDNA detected in 95% (39/41). Baseline ctDNA levels correlated with R-IPI scores and stage. ctDNA clearance during first-line therapy was predictive of improved therapy responses and outcomes (EFS, HR: 6.5, 95% CI: 1.9-22, p=0.003 and OS, HR: 22, 95% CI: 2.5-191, p=0.005). Furthermore, 48% (13/27) of patients cleared their ctDNA following the first cycle of treatment. Patients who cleared their ctDNA, irrespective of their R-IPI score, had superior outcomes compared to ctDNA-positive patients. ctDNA clearance outperformed other factors associated with EFS in multivariate analysis (HR: 49.76, 95% CI:1.1-2225.6, p=0.044). Finally, ctDNA clearance predicted complete response (CR)/no evidence of disease (NED) on average 97 days (range: 0-14.7 months) ahead of imaging/biopsy.

Conclusion

ctDNA testing in patients with DLBCL is predictive of patient outcomes and may enable personalized surveillance, intervention, and/or trial options.

Informations de copyright

Copyright © 2024 Narkhede, Tomassetti, Iqbal, Tin, Rivero-Hinojosa, George, Widden, Benrud, Malhotra, Rodriguez and Liu.

Déclaration de conflit d'intérêts

MN reports research funding from TG therapeutics, Genmab, Genentech, Roche, Gilead, Gilead/forty-seven, EUSA pharmaceuticals, Seagen Inc. and advisory support to TG therapeutics and ADC therapeutics. ST reports research funding from Novartis, Beigene, Rigel, SeaGene, Merck, Principia. AT, SR-H, GG, MM, AR, and ML are employees at Natera, Inc. with stock or options to own stock in the company. HW, RB, are former employees of Natera. ML reports Grants/Contracts: Funding to Institution Mayo from: Eisai, Exact Sciences, Genentech, Genomic Health, GRAIL, Menarini Silicon Biosystems, Merck, Novartis, Seattle Genetics, Tesaro; Travel Support Reimbursement from AstraZeneca, Genomic Health, Ionis; Ad hoc advisory board meetings. All funds to Mayo Clinic. No personal compensation from: AstraZeneca, Celgene, Roche/Genentech, Genomic Health, GRAIL, Ionis, Merck, Pfizer, Seattle Genetics, Syndax. The remaining author declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer, AB, declared a shared parent affiliation with the author MN to the handling editor at the time of review.