Molecular features encoded in the ctDNA reveal heterogeneity and predict outcome in high-risk aggressive B-cell lymphoma
(2022) In Blood 139(12). p.1863-1877- Abstract
Inadequate molecular and clinical stratification of the patients with high-risk diffuse large B-cell lymphoma (DLBCL) is a clinical challenge hampering the establishment of personalized therapeutic options. We studied the translational significance of liquid biopsy in a uniformly treated trial cohort. Pretreatment circulating tumor DNA (ctDNA) revealed hidden clinical and biological heterogeneity, and high ctDNA burden determined increased risk of relapse and death independently of conventional risk factors. Genomic dissection of pretreatment ctDNA revealed translationally relevant phenotypic, molecular, and prognostic information that extended beyond diagnostic tissue biopsies. During therapy, chemorefractory lymphomas exhibited... (More)
Inadequate molecular and clinical stratification of the patients with high-risk diffuse large B-cell lymphoma (DLBCL) is a clinical challenge hampering the establishment of personalized therapeutic options. We studied the translational significance of liquid biopsy in a uniformly treated trial cohort. Pretreatment circulating tumor DNA (ctDNA) revealed hidden clinical and biological heterogeneity, and high ctDNA burden determined increased risk of relapse and death independently of conventional risk factors. Genomic dissection of pretreatment ctDNA revealed translationally relevant phenotypic, molecular, and prognostic information that extended beyond diagnostic tissue biopsies. During therapy, chemorefractory lymphomas exhibited diverging ctDNA kinetics, whereas end-of-therapy negativity for minimal residual disease (MRD) characterized cured patients and resolved clinical enigmas, including false residual PET positivity. Furthermore, we discovered fragmentation disparities in the cell-free DNA that characterize lymphoma-derived ctDNA and, as a proof-of-concept for their clinical application, used machine learning to show that end-of-therapy fragmentation patterns predict outcome. Altogether, we have discovered novel molecular determinants in the liquid biopsy that can noninvasively guide treatment decisions.
(Less)
- author
- publishing date
- 2022-03
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood
- volume
- 139
- issue
- 12
- pages
- 15 pages
- publisher
- American Society of Hematology
- external identifiers
-
- scopus:85126847881
- pmid:34932792
- ISSN
- 0006-4971
- DOI
- 10.1182/blood.2021012852
- language
- English
- LU publication?
- no
- id
- a5bbdb8d-4691-40c9-87f5-0eddae2b8d13
- date added to LUP
- 2022-04-19 14:24:47
- date last changed
- 2024-06-16 21:17:02
@article{a5bbdb8d-4691-40c9-87f5-0eddae2b8d13,
abstract = {{<p>Inadequate molecular and clinical stratification of the patients with high-risk diffuse large B-cell lymphoma (DLBCL) is a clinical challenge hampering the establishment of personalized therapeutic options. We studied the translational significance of liquid biopsy in a uniformly treated trial cohort. Pretreatment circulating tumor DNA (ctDNA) revealed hidden clinical and biological heterogeneity, and high ctDNA burden determined increased risk of relapse and death independently of conventional risk factors. Genomic dissection of pretreatment ctDNA revealed translationally relevant phenotypic, molecular, and prognostic information that extended beyond diagnostic tissue biopsies. During therapy, chemorefractory lymphomas exhibited diverging ctDNA kinetics, whereas end-of-therapy negativity for minimal residual disease (MRD) characterized cured patients and resolved clinical enigmas, including false residual PET positivity. Furthermore, we discovered fragmentation disparities in the cell-free DNA that characterize lymphoma-derived ctDNA and, as a proof-of-concept for their clinical application, used machine learning to show that end-of-therapy fragmentation patterns predict outcome. Altogether, we have discovered novel molecular determinants in the liquid biopsy that can noninvasively guide treatment decisions.</p>}},
author = {{Meriranta, Leo and Alkodsi, Amjad and Pasanen, Annika and Lepistö, Maija and Mapar, Parisa and Blaker, Yngvild Nuvin and Jørgensen, Judit and Karjalainen-Lindsberg, Marja Liisa and Fiskvik, Idun and Mikalsen, Lars Tore G. and Autio, Matias and Björkholm, Magnus and Jerkeman, Mats and Fluge, Øystein and Brown, Peter and Jyrkkiö, Sirkku and Holte, Harald and Pitkänen, Esa and Ellonen, Pekka and Leppä, Sirpa}},
issn = {{0006-4971}},
language = {{eng}},
number = {{12}},
pages = {{1863--1877}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{Molecular features encoded in the ctDNA reveal heterogeneity and predict outcome in high-risk aggressive B-cell lymphoma}},
url = {{http://dx.doi.org/10.1182/blood.2021012852}},
doi = {{10.1182/blood.2021012852}},
volume = {{139}},
year = {{2022}},
}