Early real-world (RW) experience with a multi-cancer early detection (MCED) test.

person Candace Westgate Adventist Health, Saint Helena, CA info_outline Candace Westgate, Dallas Kingsbury, Martin Poliak, Jordan Lipton, Matthew McMillin, Louis B. Malinow, Marc Ryan Matrana, John F. Beausang, Geoff Stanley, Rita Shaknovich, Jeffrey M. Venstrom, Kathryn Kurtzman, Vershalee Shukla

Authors person Candace Westgate Adventist Health, Saint Helena, CA info_outline Candace Westgate, Dallas Kingsbury, Martin Poliak, Jordan Lipton, Matthew McMillin, Louis B. Malinow, Marc Ryan Matrana, John F. Beausang, Geoff Stanley, Rita Shaknovich, Jeffrey M. Venstrom, Kathryn Kurtzman, Vershalee Shukla Organizations Adventist Health, Saint Helena, CA, Fountain Life, Naples, FL, MDVIP Medical Clinic of Houston, Houston, TX, Signature Healthcare, PLLC, Charlotte, NC, UnityPoint Clinic MDVIP, Peoria, IL, Drs. Malinow, Oster, and Malinow, Baltimore, MD, Ochsner Cancer Institute, New Orleans, LA, GRAIL, LLC, a subsidiary of Illumina, Inc., currently held separate from Illumina, Inc., under the terms of the Interim Measures Order of the European Commission dated 29 October 2021, Menlo Park, CA, Vincere Cancer Center, Scottsdale, AZ Abstract Disclosures Research Funding Pharmaceutical/Biotech Company GRAIL 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. CSDR (%) by sex and decade with most frequent top-one CSOs. <50 50-59 60-69 70-79 >80 Most Frequent First CSO (all ages; %) Male 0.2 [0.1-0.4] (14/5775) 0.5 [0.3-0.6] (41/9058) 1.2 [1.0-1.4] (95/8034) 2.3 [1.9-2.7] (119/5244) 4.0 [2.9-5.4] (44/1090) 1. Lymphoid neoplasm (21.1) 2. Prostate (16.6) 3. Colon/Rectum (15.0) 4. Head/Neck (13.4) 5. Pancreas/Gallbladder (8.0) Female 0.5 [0.3-0.7] (22/4736) 0.4 [0.3-0.6] (33/7667) 1.0 [0.7-1.2] (65/6742) 1.5 [1.2-2.0] (63/4072) 2.0 [1.1-3.3] (14/716) 1. Breast (23.9) 2. Lymphoid neoplasm (16.2) 3. Colon/Rectum (13.7) 4. Lung (10.2) 5. Uterus (9.1)