Background Non-Hodgkin lymphoma (NHL) is one of the most common cancers accounting for about 4% of all cancers. The 10-year survival rate has dramatically increased to 90% due to novel drugs including Rituximab targeting unique B-cell surface markers such as CD20 and CAR-T cells targeting CD19, however, most of these drugs are not differentiating between normal B-cells and malignant B-cells leaving the patient with low B-cell count, and susceptibility for infections. Most patients relapse, and the disease remains incurable.

Methods We developed novel protocols for the enrichment and preservation of live B-cells and T-cells from blood. The live B-cells were tested in a live cell assay with drugs approved in FL. The same B-cells as well as collected lymph node biopsies were analyzed using our clinically validated OneRNA® platform to identify new targets, and biomarkers for response and repurpose drugs approved outside FL which could then be tested in the same live cell assay. We further analyzed whole blood, B-cells, and T-cells as well as biopsies using several MRD assays longitudinally during several treatment cycles and combined the data sets.

Results We were able to identify and rank approved treatments in FL with the results of the live cell assay as well as the OneRNA® data. The data correlated with the response to treatment. The OneRNA® assay was able to identify additional approved treatment options that were then tested in the live cell assay alone and in combination with drugs approved in FL. We further demonstrated our MRD assay was able to detect disease earlier than standard-of-care molecular assays and PET scans.

Conclusions Although Follicular Lymphoma is treatable, the optimal treatment needs to be individualized based on more comprehensive biomarkers assays guiding treatment options together with MRD assays detecting response and relapse.

Hematological cancers provide the opportunity to enrich for malignant cells and test using more comprehensive biomarker assays such as OneRNA® that can guide response to treatment and test those treatments and treatment combinations on the patient’s own cells prior to treatment.

We also validated an assay for Minimal Residual Disease (MRD), which deserves further studies as a tool to refine the clinical/metabolic response and to modulate treatment intensity/duration

Finally, the OneRNA® assay provides an opportunity to identify novel targets and surface proteins that could be developed into drugs that are specifically targeting the malignant B-cells.

Ethics Approval We obtained samples from biobanks

Consent We obtained samples from biobanks