Biomarker‐adapted treatment in high‐risk large B‐cell lymphoma

作者：Sirpa Leppä, Leo Meriranta, Maare Arffman, Judit Jørgensen, Marja‐Liisa Karjalainen‐Lindsberg, Klaus Beiske, Mette Ølgod Pedersen, Kristina Drott, Annika Pasanen, Kristiina Karihtala, Susanna Mannisto, Bente Wold, Marianne Brodtkorb, Unn‐Merete Fagerli, Thomas Stauffer Larsen, Lars Munksgaard, Kaisa Sunela, Øystein Fluge, Sirkku Jyrkkiö, Peter C. Brown, Harald Holte · 发表于：HemaSphere · 年份：2025 · DOI：10.1002/hem3.70139 · 被引用次数：6 · 研究领域：Lymphoma Diagnosis and Treatment、Chronic Lymphocytic Leukemia Research、CAR-T cell therapy research

Abstract 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.