Digital Gene Expression Cell of Origin Assay Shows High Prognostic Ability in Diffuse Large B-Cell Lymphoma
In a study reported in the Journal of Clinical Oncology, Scott et al found that the digital gene expression–based Lymph2Cx assay produced concordant cell of origin assignments in formalin-fixed paraffin-embedded tissue biopsies from patients with diffuse large B-cell lymphoma and showed high prognostic ability according to identification of activated B-cell–like vs germinal center B-cell–like diffuse large B-cell lymphoma.
Study Details
In the study, reproducibility of cell of origin assignment with the Lymph2Cx assay was examined using repeated sampling within tumor biopsies and changes in reagent lots. The prognostic ability of the assay was examined in pretreatment formalin-fixed paraffin-embedded tissue biopsies from 344 patients treated with rituximab (Rituxan) plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) at the British Columbia Cancer Agency.
Concordance and Prognostic Significance
The assay produced concordant cell of origin assignments in 96% of 49 repeatedly sampled tumor biopsies and 100% of 83 formalin-fixed paraffin-embedded tissue biopsies tested across reagent lots. No overt misclassification of activated B-cell–like vs germinal center B-cell–like diffuse large B-cell lymphoma was observed.
In testing of the assay in formalin-fixed paraffin-embedded tissue biopsies, patients with activated B-cell–like diffuse large B-cell lymphoma on the assay had significantly poorer time to progression, progression-free survival, disease-specific survival, and overall survival compared with patients with germinal center B-cell–like diffuse large B-cell lymphoma (P < .001 for all comparisons).
In pair-wise multivariate analyses, cell of origin on the assay was a significant predictor of time to progression, progression-free survival, disease-specific survival, and overall survival independent of International Prognostic Index (IPI) score (intermediate vs low and high vs low) and MYC/BCL2 dual expression (MYC positive/BCL2 positive vs non-MYC positive/BCL2 positive). The prognostic significance of cell of origin assignment was particularly noteworthy among patients with intermediate IPI scores and non-MYC–positive/BCL2-positive status (P < .001 for time to progression).
The investigators concluded: “Assignment of [diffuse large B-cell lymphoma cell of origin] by the Lymph2Cx assay using [formalin-fixed paraffin-embedded tissue] biopsies identifies patient groups with significantly different outcomes after R-CHOP, independent of IPI score and MYC/BCL2 dual expression.”
David W. Scott, MBChB, PhD, of British Columbia Cancer Research Centre, is the corresponding author of the Journal of Clinical Oncology article.
The study was supported by the Terry Fox Foundation and British Columbia Cancer Foundation. For full disclosures of the study authors, visit jco.ascopubs.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
