Prompt assessment of tumor load and treatment response in patients with lymphoma by a blood-based multiomics approach.

e19547 Background: Lymphomas represent a diverse group of diseases that arise from a clonal proliferation of lymphocytes. Periodic imaging is the current standard of care for clinical evaluation of treatment response for lymphoma patients, but It bears obvious shortcomings. Therefore, more accurate method is needed to evaluate treatment effect of Lymphoma. Methods: We present a real-time blood-based treatment response monitoring assay SeekInClarity to assess tumor load and response to varied treatment protocols in patients with lymphoma. A novel multidimensional molecular tumor burden (MTB) model was utilized. Copy number aberrations (CNAs) and fragment size (FS) patterns across the genome from sWGS data and levels of 7 PTMs (AFP, CEA, CA153, CA125, CA199, CYFRA21-1, CA724) are exploited to establish the MTB model. Patients with lymphoma were radiological assessed at baseline and reassessed regularly after treatment. The patients also had 10 ml venous blood samples collected for SeekInClarity at baseline and every two treatment cycles. Results: At baseline, 64.5% (80/124) patients were tested positive by SeekInClarity, implying the high MTB. In particular, genome-wide or focal CNA patterns were observed in 45.2% patients, and FS profile abnormality was witnessed from 42.5% patients, indicating both features are fundamental and ubiquitous surrogates of tumor burden. Elevated level of PTMs was also reported from 23.4% patients. All patients received various combination therapies with chemotherapies or immunotherapies as the backbone, and evaluated efficacy by clinical imaging. MTB evaluations of patients who underwent the follow-up SeekinClarity were compared with clinical imaging results. For the 44 patients who had negative MTB at baseline, 33 of them were performed following SeekinClarity and kept negative after treatment, and their imaging evaluations all showed remarkably curative effect. Furthermore, in the 80 patients with positive MTB, 57 patients were performed subsequent SeekinClarity tests, and a concordance of 81.6% was achieved with clinical evaluation. In addition, there was an 18.8% discordance between imaging evaluation and SeekinClarity. For these who had clinical partial response but unchanged or higher MTB, more tests and clinical evaluations are needed to assure the true clinical outcomes. Conclusions: This proof-of-concept study demonstrated SeekInClarity, a non-invasive, multidimensional multi-omics blood-based assay, can promptly evaluate the treatment response of patients with lymphoma. By implementing this assay, the dynamic change of MTB can help physicians to make well-informed decisions on the upcoming therapeutic strategies for each patient in conjunction with imaging. This study is still ongoing, and more cases and more time points are included to demonstrate the clinical performance of the assay.