Integrating genetic subtypes with PET scan monitoring to predict outcome in diffuse large B-cell lymphoma

Matías S. Mendeville; Jurriaan Janssen; G. Tjitske Los-de Vries; Erik van Dijk; Julia Richter; Marcel Nijland; Margaretha G.M. Roemer; Phylicia Stathi; Nathalie J. Hijmering; Reno Bladergroen; Diego A. Pelaz; Arjan Diepstra; Corinne J. Eertink; Coreline N. Burggraaff; Yongsoo Kim; Pieternella J. Lugtenburg; Anke van den Berg; Alexandar Tzankov; Stefan Dirnhofer; Ulrich Dührsen; Andreas Hüttmann; Wolfram Klapper; Josée M. Zijlstra; Bauke Ylstra; Daphne de Jong

doi:10.1038/s41467-024-55614-y

Integrating genetic subtypes with PET scan monitoring to predict outcome in diffuse large B-cell lymphoma

Matías S. Mendeville
, Jurriaan Janssen
, G. Tjitske Los-de Vries
, Erik van Dijk
, Julia Richter
, Marcel Nijland
, Margaretha G.M. Roemer
, Phylicia Stathi
, Nathalie J. Hijmering
, Reno Bladergroen
, Diego A. Pelaz
, Arjan Diepstra
, Corinne J. Eertink
, Coreline N. Burggraaff
, Yongsoo Kim
, Pieternella J. Lugtenburg
, Anke van den Berg
, Alexandar Tzankov
, Stefan Dirnhofer
, Ulrich Dührsen

Andreas Hüttmann, Wolfram Klapper, Josée M. Zijlstra, Bauke Ylstra^*, Daphne de Jong

^*Corresponding author for this work

Hematology

Amsterdam UMC
Kiel University
University Medical Centre Groningen
University of Basel
University Hospital Essen

Research output: Contribution to journal › Article › Academic › peer-review

8 Citations (Scopus)

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Abstract

Next Generation Sequencing-based subtyping and interim- and end of treatment positron emission tomography (i/eot-PET) monitoring have high potential for upfront and on-treatment risk assessment of diffuse large B-cell lymphoma patients. We performed Dana Farber Cancer Institute (DFCI) and LymphGen genetic subtyping for the HOVON84 (n = 208, EudraCT-2006-005174-42) and PETAL (n = 204, EudraCT-2006-001641-33) trials retrospectively combined with DFCI genetic data (n = 304). For all R-CHOP treated patients (n = 592), C5/MCD- and C2/A53-subtypes show significantly worse outcome independent of the international prognostic index. For all subtypes, adverse prognostic value of i/eot-PET-positive status is confirmed. Consistent with frequent primary refractory disease, only 67% C2 patients become eot-PET-negative versus 81-88% for other subtypes. Indicative of high relapse rates, outcome of C5 i/eot-PET-negative patients remains significantly worse in HOVON-84, which trend validates in the PETAL and SAKK38-07 trials (NCT00544219). These results show the added value of integrated genetic subtyping and PET monitoring for prognostic stratification and subtype-specific trial design.

Original language	English
Article number	109
Journal	Nature Communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-024-55614-y
Publication status	Published - 2 Jan 2025

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SDG 3 Good Health and Well-being

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Mendeville, M. S., Janssen, J., Los-de Vries, G. T., van Dijk, E., Richter, J., Nijland, M., Roemer, M. G. M., Stathi, P., Hijmering, N. J., Bladergroen, R., Pelaz, D. A., Diepstra, A., Eertink, C. J., Burggraaff, C. N., Kim, Y., Lugtenburg, P. J., van den Berg, A., Tzankov, A., Dirnhofer, S., ... de Jong, D. (2025). Integrating genetic subtypes with PET scan monitoring to predict outcome in diffuse large B-cell lymphoma. Nature Communications, 16(1), Article 109. https://doi.org/10.1038/s41467-024-55614-y

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title = "Integrating genetic subtypes with PET scan monitoring to predict outcome in diffuse large B-cell lymphoma",

abstract = "Next Generation Sequencing-based subtyping and interim- and end of treatment positron emission tomography (i/eot-PET) monitoring have high potential for upfront and on-treatment risk assessment of diffuse large B-cell lymphoma patients. We performed Dana Farber Cancer Institute (DFCI) and LymphGen genetic subtyping for the HOVON84 (n = 208, EudraCT-2006-005174-42) and PETAL (n = 204, EudraCT-2006-001641-33) trials retrospectively combined with DFCI genetic data (n = 304). For all R-CHOP treated patients (n = 592), C5/MCD- and C2/A53-subtypes show significantly worse outcome independent of the international prognostic index. For all subtypes, adverse prognostic value of i/eot-PET-positive status is confirmed. Consistent with frequent primary refractory disease, only 67\% C2 patients become eot-PET-negative versus 81-88\% for other subtypes. Indicative of high relapse rates, outcome of C5 i/eot-PET-negative patients remains significantly worse in HOVON-84, which trend validates in the PETAL and SAKK38-07 trials (NCT00544219). These results show the added value of integrated genetic subtyping and PET monitoring for prognostic stratification and subtype-specific trial design.",

author = "Mendeville, \{Mat{\'i}as S.\} and Jurriaan Janssen and \{Los-de Vries\}, \{G. Tjitske\} and \{van Dijk\}, Erik and Julia Richter and Marcel Nijland and Roemer, \{Margaretha G.M.\} and Phylicia Stathi and Hijmering, \{Nathalie J.\} and Reno Bladergroen and Pelaz, \{Diego A.\} and Arjan Diepstra and Eertink, \{Corinne J.\} and Burggraaff, \{Coreline N.\} and Yongsoo Kim and Lugtenburg, \{Pieternella J.\} and \{van den Berg\}, Anke and Alexandar Tzankov and Stefan Dirnhofer and Ulrich D{\"u}hrsen and Andreas H{\"u}ttmann and Wolfram Klapper and Zijlstra, \{Jos{\'e}e M.\} and Bauke Ylstra and \{de Jong\}, Daphne",

note = "{\textcopyright} The Author(s) 2024.",

year = "2025",

month = jan,

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doi = "10.1038/s41467-024-55614-y",

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Mendeville, MS, Janssen, J, Los-de Vries, GT, van Dijk, E, Richter, J, Nijland, M, Roemer, MGM, Stathi, P, Hijmering, NJ, Bladergroen, R, Pelaz, DA, Diepstra, A, Eertink, CJ, Burggraaff, CN, Kim, Y, Lugtenburg, PJ, van den Berg, A, Tzankov, A, Dirnhofer, S, Dührsen, U, Hüttmann, A, Klapper, W, Zijlstra, JM, Ylstra, B & de Jong, D 2025, 'Integrating genetic subtypes with PET scan monitoring to predict outcome in diffuse large B-cell lymphoma', Nature Communications, vol. 16, no. 1, 109. https://doi.org/10.1038/s41467-024-55614-y

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T1 - Integrating genetic subtypes with PET scan monitoring to predict outcome in diffuse large B-cell lymphoma

AU - Mendeville, Matías S.

AU - Janssen, Jurriaan

AU - Los-de Vries, G. Tjitske

AU - van Dijk, Erik

AU - Richter, Julia

AU - Nijland, Marcel

AU - Roemer, Margaretha G.M.

AU - Stathi, Phylicia

AU - Hijmering, Nathalie J.

AU - Bladergroen, Reno

AU - Pelaz, Diego A.

AU - Diepstra, Arjan

AU - Eertink, Corinne J.

AU - Burggraaff, Coreline N.

AU - Kim, Yongsoo

AU - Lugtenburg, Pieternella J.

AU - van den Berg, Anke

AU - Tzankov, Alexandar

AU - Dirnhofer, Stefan

AU - Dührsen, Ulrich

AU - Hüttmann, Andreas

AU - Klapper, Wolfram

AU - Zijlstra, Josée M.

AU - Ylstra, Bauke

AU - de Jong, Daphne

PY - 2025/1/2

Y1 - 2025/1/2

N2 - Next Generation Sequencing-based subtyping and interim- and end of treatment positron emission tomography (i/eot-PET) monitoring have high potential for upfront and on-treatment risk assessment of diffuse large B-cell lymphoma patients. We performed Dana Farber Cancer Institute (DFCI) and LymphGen genetic subtyping for the HOVON84 (n = 208, EudraCT-2006-005174-42) and PETAL (n = 204, EudraCT-2006-001641-33) trials retrospectively combined with DFCI genetic data (n = 304). For all R-CHOP treated patients (n = 592), C5/MCD- and C2/A53-subtypes show significantly worse outcome independent of the international prognostic index. For all subtypes, adverse prognostic value of i/eot-PET-positive status is confirmed. Consistent with frequent primary refractory disease, only 67% C2 patients become eot-PET-negative versus 81-88% for other subtypes. Indicative of high relapse rates, outcome of C5 i/eot-PET-negative patients remains significantly worse in HOVON-84, which trend validates in the PETAL and SAKK38-07 trials (NCT00544219). These results show the added value of integrated genetic subtyping and PET monitoring for prognostic stratification and subtype-specific trial design.

AB - Next Generation Sequencing-based subtyping and interim- and end of treatment positron emission tomography (i/eot-PET) monitoring have high potential for upfront and on-treatment risk assessment of diffuse large B-cell lymphoma patients. We performed Dana Farber Cancer Institute (DFCI) and LymphGen genetic subtyping for the HOVON84 (n = 208, EudraCT-2006-005174-42) and PETAL (n = 204, EudraCT-2006-001641-33) trials retrospectively combined with DFCI genetic data (n = 304). For all R-CHOP treated patients (n = 592), C5/MCD- and C2/A53-subtypes show significantly worse outcome independent of the international prognostic index. For all subtypes, adverse prognostic value of i/eot-PET-positive status is confirmed. Consistent with frequent primary refractory disease, only 67% C2 patients become eot-PET-negative versus 81-88% for other subtypes. Indicative of high relapse rates, outcome of C5 i/eot-PET-negative patients remains significantly worse in HOVON-84, which trend validates in the PETAL and SAKK38-07 trials (NCT00544219). These results show the added value of integrated genetic subtyping and PET monitoring for prognostic stratification and subtype-specific trial design.

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DO - 10.1038/s41467-024-55614-y

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Integrating genetic subtypes with PET scan monitoring to predict outcome in diffuse large B-cell lymphoma

Abstract

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