Nature Communications (Jan 2025)

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
https://doi.org/10.1038/s41467-024-55614-y
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 12

Abstract

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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.