Early Real-World (RW) Experience with a Multi-Cancer Early Detection (MCED) Test.

10519 Background: An MCED test (Galleri, GRAIL, LLC, Menlo Park, CA) intended to complement recommended screening has been in clinical use since 04/2021. Here, we report RW clinical experience across age, sex, ordering site, and use case with the initial ~53,000 tests. Methods: This cell-free DNA-based MCED test uses a targeted methylation assay and a machine learning classification algorithm to detect a cancer signal (CS) and predict CS origin (CSO). This report includes tests returned from 04/20/2021 to 12/31/2022 on individuals aged ≥22 years (yrs) and excludes tests from clinical studies and sites limiting external data sharing, and repeat tests. Systematic collection of outcomes for cases with a “CS detected” (CSD) result was completed for a limited subset and continues via a rigorously controlled quality assurance (QA) program. Results: Tests were ordered and processed from across all US states (results returned, 98.9%; mean turnaround time, 6.7 business days). Among the 53,134 tests with results returned, CSD rate (CSDR) was was 1.0% (95% CI, 0.9-1.0; 510/53134), generally higher in males (1.1% [1.0-1.2; 313/29201]) vs females (0.8% [0.7-0.9; 197/23933]), and comparable to expected CSDR (males 1.07%; females 0.96%) as modeled based on MCED test performance and cancer incidence from SEER. CSDR increased with age (Table), which was a significant predictor of CSDR (p < 2e-13). In males and females, 67.4% and 61.9% of CSOs represented cancers without (w/o) recommended population screening, respectively. Early data from the QA program from an initial limited subset of CSD cases showed that a CSD result was associated with a diagnosis of invasive cancer across multiple cancers (eg, anus, breast, esophagus, head and neck, liver/bile duct, lymphoma, ovary, pancreas, plasma cell neoplasm, prostate, sarcoma), including stage I and II cancers. Conclusions: RW experience with the MCED test was consistent with previous large-scale clinical studies with an average CSDR of 1.0%, which increased with age. The test detected a CS and predicted CSO across multiple cancers, including early-stage cancers and cancers w/o recommended screening. This indicates that the MCED test can reliably detect a CS, which is essential to support population screening. Follow-up of CSD cases is ongoing through the QA program and will allow for future reporting of RW outcomes. [Table: see text]