TY - JOUR
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
N1 - © 2024. The Author(s).
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.
KW - Humans
KW - Lymphoma, Large B-Cell, Diffuse/genetics
KW - Positron-Emission Tomography/methods
KW - Male
KW - Female
KW - Middle Aged
KW - Cyclophosphamide/therapeutic use
KW - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
KW - Retrospective Studies
KW - Prognosis
KW - Rituximab/therapeutic use
KW - Aged
KW - Prednisone/therapeutic use
KW - Adult
KW - Vincristine/therapeutic use
KW - Doxorubicin/therapeutic use
KW - Treatment Outcome
KW - High-Throughput Nucleotide Sequencing/methods
KW - Young Adult
U2 - 10.1038/s41467-024-55614-y
DO - 10.1038/s41467-024-55614-y
M3 - Article
C2 - 39747123
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 109
ER -