ctDNA as a Noninvasive Biomarker in High-Risk LBCL

Intensified immunochemotherapy combined with early systemic high-dose methotrexate (HD-Mtx) could benefit young patients (pts) with high-risk large B-cell lymphoma (LBCL).

In this study, pts under 65 with high-risk aggressive B-cell lymphoma were enrolled in the Nordic Lymphoma Group phase II trial (NLG-LBC-06). They underwent two cycles of R-CHOP-21 with HD-Mtx on day 15, followed by four courses of R-CHOEP-14 (if no biological risk factors were present) or four courses of dose-adjusted EPOCH-R (if biological risk factors based on C-MYC translocation, C-MYC and BCL2 translocation (double hit), 17p/TP53 deletion, co-expression of MYC and BCL2, P53+ and/or CD5+ were present). All pts received one course of R-HD-cytarabine, and plasma samples were collected at various timepoints. ctDNA was analyzed as an exploratory noninvasive biomarker. A custom capture-based gene panel with an in-house adapted duplex strategy and sequencing was used in the study.

Of the 123 eligible pts, 61 were deemed high-risk and 62 low-risk. The median follow-up of 37 months (1–63) revealed that 3-year failure free survival (FFS), progression free survival (PFS), and overall survival (OS) rates for the pts were 79%, 84%, and 90%, respectively. The survival rates were comparable in biologically high- and low-risk patients. Multivariable analysis identified 17p/TP53 deletion as the only risk factor for progression and death. Despite varying levels of pretreatment ctDNA and mutational content among pts, there was no difference in ctDNA burden between the high-risk and low-risk groups. Nevertheless, pts with high pretreatment ctDNA levels and TP53 mutations had worse survival outcomes. ctDNA profiling of the mid- and end-of-therapy samples is still continuing, and the results will be shared.

Intensified immunochemotherapy benefits high-risk LBCL pts, except those with 17p/TP53 deletion, TP53 mutations, or high ctDNA burden. The study highlighted the role of ctDNA as a noninvasive biomarker to improve risk stratification and guide treatment decisions for high-risk LBCL pts.

Source: https://onlinelibrary.wiley.com/doi/10.1002/hon.3163_21

Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03293173

Leppa, S., Meriranta, L., Arffman, M., Jørgensen, J., Karjalainen-Lindsberg, M., Beiske, K., Pedersen, M., Drott, K., Fluge, Ø., Jyrkkiö, S., Brown, P., & Holte, H. BIOMARKER-DRIVEN TREATMENT STRATEGY IN HIGH-RISK LARGE B-CELL LYMPHOMA (NLG-LBC-06 PHASE II TRIAL): IMPACT OF CTDNA AND TP53 ABERRATIONS ON CLINICAL OUTCOME. Hematological Oncology, 41, 51-52. https://doi.org/10.1002/hon.3163_21