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 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 Berg, Alexandar Tzankov, Stefan Dirnhofer, Ulrich Dührsen, Andreas Hüttmann, Wolfram Klapper, Josée M. Zijlstra, Bauke Ylstra () and Daphne Jong
Additional contact information
Matías S. Mendeville: location VUmc
Jurriaan Janssen: location VUmc
G. Tjitske Los- de Vries: location VUmc
Erik Dijk: location VUmc
Julia Richter: Campus Kiel
Marcel Nijland: University Medical Centre Groningen
Margaretha G. M. Roemer: location VUmc
Phylicia Stathi: location VUmc
Nathalie J. Hijmering: location VUmc
Reno Bladergroen: location VUmc
Diego A. Pelaz: location VUmc
Arjan Diepstra: University Medical Centre Groningen
Corinne J. Eertink: location VUmc
Coreline N. Burggraaff: location VUmc
Yongsoo Kim: location VUmc
Pieternella J. Lugtenburg: University Medical Center Rotterdam
Anke Berg: University Medical Centre Groningen
Alexandar Tzankov: University of Basel and University Hospital Basel
Stefan Dirnhofer: University of Basel and University Hospital Basel
Ulrich Dührsen: University Hospital Essen
Andreas Hüttmann: University Hospital Essen
Wolfram Klapper: Campus Kiel
Josée M. Zijlstra: location VUmc
Bauke Ylstra: location VUmc
Daphne Jong: location VUmc

Nature Communications, 2025, vol. 16, issue 1, 1-12

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-024-55614-y

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