A1 Refereed original research article in a scientific journal
Biomarker‐adapted treatment in high‐risk large B‐cell lymphoma
Authors: Leppä, Sirpa; Meriranta, Leo; Arffman, Maare; Jørgensen, Judit; Karjalainen‐Lindsberg, Marja‐Liisa; Beiske, Klaus; Pedersen, Mette; Drott, Kristina; Pasanen, Annika; Karihtala, Kristiina; Mannisto, Susanna; Wold, Bente; Brodtkorb, Marianne; Fagerli, Unn‐Merete; Larsen, Thomas Stauffer; Munksgaard, Lars; Sunela, Kaisa; Fluge, Øystein; Jyrkkiö, Sirkku; Brown, Peter; Holte, Harald
Publisher: Wiley
Publication year: 2025
Journal: HemaSphere
Journal name in source: HemaSphere
Article number: e70139
Volume: 9
Issue: 5
ISSN: 2572-9241
eISSN: 2572-9241
DOI: https://doi.org/10.1002/hem3.70139
Web address : https://doi.org/10.1002/hem3.70139
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/492262649
Survival rates for patients with high-risk large B-cell lymphoma (LBCL), particularly those with biological risk factors, remain inadequate. We conducted a biomarker-driven phase II trial involving 123 high-risk patients aged 18–64 with LBCL. Based on their biological risk profiles, patients received either R-CHOEP-14 (without risk factors) or DA-EPOCH-R-based regimens (with risk factors). Biological high-risk factors included C-MYC translocation, C-MYC and BCL2 co-translocation, 17p/TP53 deletion, co-expression of MYC and BCL2, and P53 and/or CD5 immunopositivity. Additionally, we evaluated circulating tumor DNA (ctDNA) kinetics during therapy. Sixty-one patients (50%) were classified into biologically high-risk group. Three-year failure-free survival and overall survival rates for the entire study population were 79% and 88%, respectively. DA-EPOCH-R did not improve survival compared to our previous trial, where patients with the same biological risk factor criteria received R-CHOEP-14-based therapy. High pretreatment ctDNA levels, 17p/TP53 deletion, and TP53 mutations were associated with worse outcomes. In contrast, ctDNA negativity at the end of therapy (EOT) was indicative of a cure and effectively addressed false residual PET positivity. The findings demonstrate promising survival for high-risk LBCL patients, aside from those with TP53 aberrations, high ctDNA levels, and/or EOT ctDNA positivity.
Downloadable publication This is an electronic reprint of the original article. |  |
Funding information in the publication:
This study was funded by the Research Council of Finland, Finnish Cancer Organizations, iCAN Flagship, Nordic Cancer Union, Southern Finland Regional Cancer Center (FICAN South), Sigrid Juselius Foundation, and Helsinki and Uusimaa Hospital District. Open access was funded by Helsinki University Library.
