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 L...

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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-55614-y
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Summary: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.
ISSN:2041-1723