178 Scalable liquid biopsy assay for treatment optimization and MRD detection in lymphoma and its validation in live cell assays

<h3>Background</h3> 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 such as Rituximab targeting B-cell surface markers CD20 and CAR-T cells targeting CD19. However, none of these drugs differentiate between normal B-cells and malignant B-cells leaving the patient with low B-cell count susceptibility to infections. Most patients relapse, and the disease remains incurable.¹ Categorization of lymphoma type is based on the visual presentation and location of the cells, not the underlying mechanism that drives the tumor. The oncologist has access to multiple first-line of treatment options, however without biomarker guidance treatment selection becomes trial and error with the patient’s life in the balance. Some patients undergo one treatment, then the next treatment, and then the third treatment. Eventually, they die from their disease or the collateral damage from the treatments. To change this paradigm biomarkers for first line selection and beyond are warranted. <h3>Methods</h3> Genomic Expression developed novel protocols for the enrichment and preservation of live B-cells and T-cells from blood shipped at room temperature. The B-cells were cryopreserved and later analyzed using Genomic Expressions clinically validated RNA-seq platform, OneRNA®, to identify biomarkers for response to drugs which were then tested in a live cell assay.^2-4 Whole blood samples were also tested for Minimal Residual Disease (MRD) longitudinally during several treatment cycles. <h3>Results</h3> OneRNA® was able to identify FDA-approved drugs and confirm response in the live B cell assay. The data correlated with the patient’s response to treatment. The MRD data correlated better with response than the standard of care assay. <h3>Conclusions</h3> Although lymphoma is treatable, the optimal treatment needs to be individualized based on more comprehensive biomarkers assays together with MRD assays monitoring for response and relapse.⁵ 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 before treatment selection. This setup also facilitates the testing and optimization of individualized immune therapies and combinatorial treatments. Furthermore, the OneRNA® platform identifies novel targets and assists in the design of effective combinatorial adaptive n-of-one studies. <h3>Acknowledgements</h3> This project was done in collaboration with Dana Faber Cancer Institute. <h3>References</h3> Qualls D, Salles G. Prospects in the management of patients with follicular lymphoma beyond first-line therapy. <i>Haematologica</i> 2022;<b>107</b>(1):19-34. doi:10.3324/haematol.2021.278717 Novel RNA-seqPlatform Improve Patient Outcome in Clinical Oncology and enable implementationof AI in the clinic, poster presented at the SITC 2021 . https://bit.ly/SITC2021OneRNA Novel RNA-seqPlatform Enables Repurposing of Approved Drugs in Rare Cancers, ImprovingOutcomes, Poster presented at SITC 2022 . https://tinyurl.com/2022SITCRareCancer Novel RNA-seqPlatform Enabling Treatment Decisions and Improved Patient Outcome, Poster presented at the NYAS Frontier in Immune Oncology 2022. https://bit.ly/OneRNA2022NYAS Letai A, Bassik MC, Walensky LD, Sorcinelli MD, Weiler S, Korsmeyer SJ. Distinct BH3 domains either sensitize or activate mitochondrial apoptosis, serving as prototype cancer therapeutics. <i>Cancer Cell</i> 2002;<b>2</b>(3):183-192. doi:10.1016/s1535-6108(02)00127-7 <h3>Consent</h3> We used the decision tool from NCI to determine if our study should be classified as human subject research https://grants.nih.gov/policy/humansubjects/hs-decision.htm This study does not involve any intervention nor interaction with subjects for the collection of biospecimens or data. All samples have been de-identified and do not contain any identifiable private information All biospecimens are obtained from commercial biobanks or from providers that are prohibited from releasing identifiers by established regulations or policies. We will never be able to link the biospecimens/information directly to identifiable private information of living individuals. The providers do not meet the definition of an ‘investigator’ in our research and they are not key personnel on this proposal merely providers of samples.