NGS-determined molecular markers and disease burden metrics from ctDNA correlate with PFS in previously untreated DLBCL

Abstract

Personalized risk stratification and treatment may help improve outcomes among patients with diffuse large B-cell lymphoma (DLBCL). We developed a next-generation sequencing (NGS)-based method to assess a range of potential prognostic indicators, and evaluated it using pretreatment plasma samples from 310 patients with previously untreated DLBCL from the GOYA trial (NCT01287741). Variant calls and DLBCL subtyping with the plasma-based method were concordant with corresponding tissue-based methods. Patients with a tumor burden greater than the median (p = .003) and non-germinal center B-cell-like (non-GCB) DLBCL (p = .049) had worse progression-free survival than patients with a tumor burden less than the median or GCB DLBCL. Multi-factor assessment combining orthogonal features from a single pretreatment plasma sample has promise as a prognostic indicator in this setting (p = .085). This minimally invasive plasma-based NGS assay could enable comprehensive prognostic assessment of patients in a clinical setting, with greater accessibility than current methods.

Keywords:

• DLBCL
• circulating tumor DNA
• next-generation sequencing
• biomarkers
• GOYA

Acknowledgments

The authors thank the patients and their families, all GOYA trial team members, and investigators. GOYA was supported by F. Hoffmann-La Roche Ltd. Third-party medical writing assistance under the direction of Ehsan Tabari was provided by Helen Cathro, PhD, of Ashfield MedComms, an Inizio company, and was funded by F. Hoffmann-La Roche Ltd.

Authors’ contributions

Study design: ET, AL, KTL. Study conduct: ET, AL, CB, KTL. Data collection: SLS, JPL, TN. Data analysis: ET, CB, HL. Data interpretation: ET, AL, CB, DMK, AB, TN, JP.

Disclosure statement

E.T is employed by Freenome, formerly employed by Roche Sequencing Solutions and has equity ownership interests in Freenome. A.F.L is employed by Freenome, formerly employed by Roche Sequencing Solutions, and has equity ownership interests in Freenome. H.L is employed by Roche Sequencing Solutions and has other financial relationships with Veractye (spouse). C.R.B is employed by Genentech, Inc. and has equity ownership interests in F. Hoffmann-La Roche Ltd. S.L.S is employed by Roche Sequencing Solutions. J.P.L is employed by Roche Sequencing Solutions. D.M.K reports consultancy with Roche Molecular, Genentech, Inc., and equity ownership in Foresight Diagnostics. A.B, T.G.N and J.M.P are employed by and have equity ownership interests in F. Hoffmann-La Roche Ltd. K.T.L is employed by Illumina Inc., formerly employed by F. Hoffmann-La Roche Ltd., and has equity ownership interests in Natera and Illumina Inc.

Data availability statement

Data are not shared in an unrestricted way, but individual requests for data sharing will be assessed on a case-by-case basis.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.