627. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas) —

Results from Retrospective/Observational Studies: Biomarkers and Prognostication in Aggressive B-Cell Non-Hodgkin Lymphomas

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Adam J Olszewski, Anna D Chorzalska, Max Petersen, et al. 

Authors Conclusion from the Abstract: In this proof-of-concept study, the NGS-MRD CSF assay showed 100% sensitivity for diagnosing intraparenchymal CNS invasion in aggressive lymphomas that were not detected in the CSF using conventional methods. In a prospective cohort of newly diagnosed pts without baseline CNS invasion but at high clinical risk for CNS relapse, the assay identified lymphoma-derived cfDNA in 42% of cases. The 100% sensitivity and 100% negative predictive value of the assay for subsequent CNS relapse warrants further prospective evaluation as a potential tool for personalizing CNS-directed prophylaxis.

Reid W Merryman, Robert A. Redd, Eleanor Taranto, et al.

Authors Conclusion from the Abstract: Identification of ctDNA using IgNGS within an ASC sample is a powerful predictor of post-ASCT relapse and provides (at least in this cohort) a better way to predict relapse than pre-ASCT PET. Detection of ctDNA in pre-ASCT plasma also appears to be predictive of relapse. In ctDNA-pos pts, given the dismal PFS, strong consideration could be given to alternative treatment strategies, e.g. CAR-T cell therapy. Furthermore, detection of ctDNA in post-ASCT plasma samples is closely associated with impending relapse, which provides an attractive platform for pre-emptive therapeutic intervention.

Alex F. Herrera, Samuel Tracy, Brandon Croft, et al.

Authors Conclusion from the Abstract: Baseline ctDNA levels were correlated with standard clinical risk factors, and were shown to have independent prognostic value for response, PFS and OS in R/R DLBCL pts treated with BR +/- pola. The degree of ctDNA change upon treatment was also correlated with response, but association with PFS needs further investigation with a larger sample size. This provides early evidence that ctDNA can be used to improve identification of R/R DLBCL pts at high risk for disease progression/relapse.

Joo Y Song, Anamarija M. Perry, Alex F. Herrera, et al.

Authors Conclusion from the Abstract: We have identified four distinct biologic subgroups of GCB DLBCL with different survival rates, and with similarities to the genomic classifications from recent large retrospective studies of DLBCL. Patients with the DH signature but no abnormalities of TP53 (GCB2), and those lacking EZH2 mutation and BCL2 translocation (GCB4), had an excellent prognosis. However, patients with an EZB-like profile (GCB3) had an intermediate prognosis, whereas those with TP53 inactivation combined with the DH signature (GCB1) had an extremely poor prognosis. We propose this as a practical schema to risk-stratify patients with GCB DLBCL. This schema provides a promising new approach to identify high-risk patients for new and innovative therapies.

Nicholas J. Boddicker, Pinkal Desai, Mithun Vinod Shah, et al.

Authors Conclusion from the Abstract: In this novel study of newly diagnosed DLBCL patients, clonal somatic mutations were identified in 6.5% of patients and were associated with inferior outcomes. Additional research is required at deeper sequencing to validate these findings and integration with tumor genomics is required to understand the prognosis of DLBCL patients with smaller clonal populations.

Jakoba J Eertink,  Tim van de Brug, Sanne E Wiegers, et al.

Authors Conclusion from the Abstract: Combining quantitative radiomics features extracted from baseline 18F-FDG PET/CT scans with components of the IPI score significantly improved identification of patients at risk of relapse at baseline. Adding radiomics features can significantly increase the efficiency of clinical trials in poor prognosis patients.