A Case-Driven Multi-Omics Analysis for Longitudinal Ibrutinib Response Evaluation of Patients With Chronic Lymphocytic Leukemia

Sólja Remisdóttir Veyhe; Marcus Høy Hansen; Oriane Cédile; Michael Boe Møller; Mie Kiszka Nielsen; Mads Thomassen; Karen Juul-Jensen; Henrik Frederiksen; Karen Dybkær; Charlotte Guldborg Nyvold

doi:10.1111/ejh.14397

A Case-Driven Multi-Omics Analysis for Longitudinal Ibrutinib Response Evaluation of Patients With Chronic Lymphocytic Leukemia

Sólja Remisdóttir Veyhe
, Marcus Høy Hansen
, Oriane Cédile
, Michael Boe Møller
, Mie Kiszka Nielsen
, Mads Thomassen
, Karen Juul-Jensen
, Henrik Frederiksen
, Karen Dybkær
, Charlotte Guldborg Nyvold

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

Abstract

Patients with chronic lymphocytic leukemia (CLL) undergoing ibrutinib treatment often experience incomplete response, yet the molecular level underlying clonal inertia remains to be explored. We investigated the molecular and clinical dynamics of CLL during 16 months of ibrutinib monotherapy by analyzing blood samples from two patients who continued having CLL cells in the peripheral blood during treatment. At diagnosis, the clonal burden within the B cell compartment was found to be 55% (pt1) and 86% (pt2) for the dominant clones. At 16 months following treatment these clones still constituted 66% and 89%, respectively. Utilizing multi-omic methodologies at the DNA and RNA levels, including single-cell transcriptomics, we aimed to establish a comprehensive framework for multi-omics analysis for longitudinal ibrutinib response evaluation. The presented study revealed genomically stable disease during ibrutinib treatment, but with intensified expression of genes involved in pathways related to apoptosis, cellular stress response, and canonical NF-κB signaling from diagnosis to 16 months of treatment.

Original language	English
Book series	European Journal of Haematology
Volume	114
Issue	6
Pages (from-to)	973-981
Number of pages	9
ISSN	0902-4506
DOIs	https://doi.org/10.1111/ejh.14397
Publication status	Published - Jun 2025
Externally published	Yes

Keywords

Adenine/analogs & derivatives
Gene Expression Profiling
Genomics/methods
Humans
Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy
Multiomics
Piperidines/therapeutic use
Protein Kinase Inhibitors/therapeutic use
Pyrazoles/therapeutic use
Pyrimidines/therapeutic use
Transcriptome
Treatment Outcome

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10.1111/ejh.14397

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Veyhe, S. R., Hansen, M. H., Cédile, O., Møller, M. B., Nielsen, M. K., Thomassen, M., Juul-Jensen, K., Frederiksen, H., Dybkær, K., & Nyvold, C. G. (2025). A Case-Driven Multi-Omics Analysis for Longitudinal Ibrutinib Response Evaluation of Patients With Chronic Lymphocytic Leukemia. European Journal of Haematology, 114(6), 973-981. https://doi.org/10.1111/ejh.14397

@article{a0d0590e1d3a4032b756e38d8a2792c3,

title = "A Case-Driven Multi-Omics Analysis for Longitudinal Ibrutinib Response Evaluation of Patients With Chronic Lymphocytic Leukemia",

abstract = "Patients with chronic lymphocytic leukemia (CLL) undergoing ibrutinib treatment often experience incomplete response, yet the molecular level underlying clonal inertia remains to be explored. We investigated the molecular and clinical dynamics of CLL during 16 months of ibrutinib monotherapy by analyzing blood samples from two patients who continued having CLL cells in the peripheral blood during treatment. At diagnosis, the clonal burden within the B cell compartment was found to be 55\% (pt1) and 86\% (pt2) for the dominant clones. At 16 months following treatment these clones still constituted 66\% and 89\%, respectively. Utilizing multi-omic methodologies at the DNA and RNA levels, including single-cell transcriptomics, we aimed to establish a comprehensive framework for multi-omics analysis for longitudinal ibrutinib response evaluation. The presented study revealed genomically stable disease during ibrutinib treatment, but with intensified expression of genes involved in pathways related to apoptosis, cellular stress response, and canonical NF-κB signaling from diagnosis to 16 months of treatment.",

keywords = "Adenine/analogs \& derivatives, Gene Expression Profiling, Genomics/methods, Humans, Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy, Multiomics, Piperidines/therapeutic use, Protein Kinase Inhibitors/therapeutic use, Pyrazoles/therapeutic use, Pyrimidines/therapeutic use, Transcriptome, Treatment Outcome",

author = "Veyhe, \{S{\'o}lja Remisd{\'o}ttir\} and Hansen, \{Marcus H{\o}y\} and Oriane C{\'e}dile and M{\o}ller, \{Michael Boe\} and Nielsen, \{Mie Kiszka\} and Mads Thomassen and Karen Juul-Jensen and Henrik Frederiksen and Karen Dybk{\ae}r and Nyvold, \{Charlotte Guldborg\}",

note = "{\textcopyright} 2025 The Author(s). European Journal of Haematology published by John Wiley \& Sons Ltd.",

year = "2025",

month = jun,

doi = "10.1111/ejh.14397",

language = "English",

volume = "114",

pages = "973--981",

journal = "European Journal of Haematology",

issn = "0902-4506",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "6",

}

A Case-Driven Multi-Omics Analysis for Longitudinal Ibrutinib Response Evaluation of Patients With Chronic Lymphocytic Leukemia. / Veyhe, Sólja Remisdóttir; Hansen, Marcus Høy; Cédile, Oriane et al.
In: European Journal of Haematology, Vol. 114, No. 6, 06.2025, p. 973-981.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - A Case-Driven Multi-Omics Analysis for Longitudinal Ibrutinib Response Evaluation of Patients With Chronic Lymphocytic Leukemia

AU - Veyhe, Sólja Remisdóttir

AU - Hansen, Marcus Høy

AU - Cédile, Oriane

AU - Møller, Michael Boe

AU - Nielsen, Mie Kiszka

AU - Thomassen, Mads

AU - Juul-Jensen, Karen

AU - Frederiksen, Henrik

AU - Dybkær, Karen

AU - Nyvold, Charlotte Guldborg

PY - 2025/6

Y1 - 2025/6

N2 - Patients with chronic lymphocytic leukemia (CLL) undergoing ibrutinib treatment often experience incomplete response, yet the molecular level underlying clonal inertia remains to be explored. We investigated the molecular and clinical dynamics of CLL during 16 months of ibrutinib monotherapy by analyzing blood samples from two patients who continued having CLL cells in the peripheral blood during treatment. At diagnosis, the clonal burden within the B cell compartment was found to be 55% (pt1) and 86% (pt2) for the dominant clones. At 16 months following treatment these clones still constituted 66% and 89%, respectively. Utilizing multi-omic methodologies at the DNA and RNA levels, including single-cell transcriptomics, we aimed to establish a comprehensive framework for multi-omics analysis for longitudinal ibrutinib response evaluation. The presented study revealed genomically stable disease during ibrutinib treatment, but with intensified expression of genes involved in pathways related to apoptosis, cellular stress response, and canonical NF-κB signaling from diagnosis to 16 months of treatment.

AB - Patients with chronic lymphocytic leukemia (CLL) undergoing ibrutinib treatment often experience incomplete response, yet the molecular level underlying clonal inertia remains to be explored. We investigated the molecular and clinical dynamics of CLL during 16 months of ibrutinib monotherapy by analyzing blood samples from two patients who continued having CLL cells in the peripheral blood during treatment. At diagnosis, the clonal burden within the B cell compartment was found to be 55% (pt1) and 86% (pt2) for the dominant clones. At 16 months following treatment these clones still constituted 66% and 89%, respectively. Utilizing multi-omic methodologies at the DNA and RNA levels, including single-cell transcriptomics, we aimed to establish a comprehensive framework for multi-omics analysis for longitudinal ibrutinib response evaluation. The presented study revealed genomically stable disease during ibrutinib treatment, but with intensified expression of genes involved in pathways related to apoptosis, cellular stress response, and canonical NF-κB signaling from diagnosis to 16 months of treatment.

KW - Adenine/analogs & derivatives

KW - Gene Expression Profiling

KW - Genomics/methods

KW - Humans

KW - Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy

KW - Multiomics

KW - Piperidines/therapeutic use

KW - Protein Kinase Inhibitors/therapeutic use

KW - Pyrazoles/therapeutic use

KW - Pyrimidines/therapeutic use

KW - Transcriptome

KW - Treatment Outcome

UR - https://www.scopus.com/pages/publications/85218683625

U2 - 10.1111/ejh.14397

DO - 10.1111/ejh.14397

M3 - Journal article

C2 - 39988467

SN - 0902-4506

VL - 114

SP - 973

EP - 981

JO - European Journal of Haematology

JF - European Journal of Haematology

IS - 6

ER -

A Case-Driven Multi-Omics Analysis for Longitudinal Ibrutinib Response Evaluation of Patients With Chronic Lymphocytic Leukemia

Abstract

Keywords

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