Abstract 5111: Prompt assessment of molecular tumor load and treatment response in patients with lymphoma by a blood-based multi-omics approach

Abstract

Abstract Here we present a real-time blood-based treatment response monitoring assay SeekInClarity to assess molecular tumor load and response to varied treatment protocols in patients with lymphoma. A novel multidimensional molecular tumor burden (MTB) model was utilized by integrating shallow whole genome sequencing (sWGS) of cfDNA and the levels of a set of plasma protein markers (PTMs) in a single blood draw. 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.Newly diagnosed patients with lymphoma were radiologically assessed at baseline and periodically reassessed after treat started as determined per standard of care routine clinical assessment. The patients also had 10 ml venous blood samples collected for SeekInClarity at baseline and every two treatment cycles.At baseline, 55(61.1%) of 90 patients were tested positive (MTB>2) by SeekInClarity, implying the high sensitivity. In particular, genome-wide or focal CNA pattern was observed from 52 of 55 positive patients, and FS profile abnormality was witnessed from 31 of 55 positive patients, indicating both features are fundamental and ubiquitous surrogates of tumor burden. Specifically, 8q24.2 is the most frequently amplified region at the baseline, which contains an important oncogene MYC. Moreover, the common regions of deletion were 1p36, 4q21 and 6q21. All these regions are involved in genes related to cancer. Elevated level of PTMs was also reported from 32 patients. All patients received varied combination therapies with chemotherapies as the backbone, and compared with clinical imaging. Patients who underwent the second and the third SeekinClarity tests mostly showed significantly decreased MTB, indicating partial response was achieved under the current regimens. Moreover, two of the patients underwent the fourth SeekInClarity test. One achieved a sustained partial response, but another had higher MTB at the fourth test so resistance may be inferred. And all the results were consistent with the clinical imaging. 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 molecular surrogates (CNA, FS and PTMs) 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 comparing to the current standard of care for clinical evaluation of treatment response for lymphoma patients. Citation Format: Xinhua Wang, Yu Chang, Zhiming Li, Yinyin Chang, Dandan Zhu, Shuaipeng Geng, Fangyuan Chang, Shiyong Li, Yan Chen, Mingzhi Zhang, Mao Mao. Prompt assessment of molecular tumor load and treatment response in patients with lymphoma by a blood-based multi-omics approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5111.