1184P - Early real-world experience with positive multi-cancer early detection (MCED) test cases and negative initial diagnostic work-up

Background

An MCED blood test (Galleri®) has been in clinical use since April 2021. It is intended for screening adults aged 50-79 yrs. Using machine learning, this MCED test analyzes targeted methylation in cell-free DNA to detect a cancer signal and predict cancer signal origin (CSO). Individuals with suspected “false positive” results are offered a retest. Here we report early clinical experience with MCED retesting.

Methods

We analyzed likelihood of a subsequent cancer diagnosis in individuals with an initial MCED test result (Test 1) of cancer signal detected (CSD) and a negative initial diagnostic evaluation, followed by a second MCED test (Retest) within 3-6 mos for most.

Results

In a real-world evidence (RWE) cohort of ∼200,000 commercial MCED tests with ∼1800 CSD results, 159 individuals (69% male, mean age 67 yr [IQR: 60-76]) were identified who match the above criteria (Table). The mean time between blood draws was 5.4 mos [IQR: 3.8-6.1]. Of these patients, 31% (50/159) had a persistent CSD and 69% (109/159) had no cancer signal detected (NCSD) on Retest. Hematologic CSOs on Test 1 had statistically higher CSD on Retest (64%, 18/28) compared to solid tumor CSOs (24%, 32/131; p

Conclusions

Early RWE shows that persistent CSD on Retest is associated with a higher risk of cancer diagnosis, suggesting the need for close monitoring and/or additional diagnostic evaluation in these patients and the value of retesting. Patients with hematologic CSOs on Test 1 were more likely to have CSD on Retest than patients with solid cancer CSOs. No subsequent cancers have been diagnosed in patients with NCSD on Retest.

Clinical trial identification

Editorial acknowledgement

Writing and editorial assistance was provided by Neva C West, PhD (NeuroWest Solutions, Chicago, IL, USA).

Legal entity responsible for the study

Grail, Llc.

Funding

Grail, Llc.

Disclosure

C. Westgate: Financial Interests, Personal, Speaker, Consultant, Advisor: Grail Llc, Myriad; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca. O. Gordon: Financial Interests, Institutional, Research Funding: Grail Llc; Financial Interests, Personal, Advisory Role: Genetic Technologies Corp. M. Margolis, R. Jiang, E.A. Klein: Financial Interests, Personal, Full or part-time Employment: Grail Llc. Y. Oh, O. Venn, S. Leake, E. Hubbell, E.T. Fung, J. Venstrom, R.S. Shaknovich: Financial Interests, Personal, Full or part-time Employment, stock ownership in Illumina, Bristol Myers Squibb, Gilead, Baxter, and Bayer: Grail Llc. D. Broyles: Financial Interests, Personal, Speaker, Consultant, Advisor: Grail Llc, Cardiogiagnostics Holdings; Financial Interests, Personal, Ownership Interest: Caralyst; Financial Interests, Personal, Officer: Imperial Diagnostics. W. Jones, J. Ferrell: Financial Interests, Personal, Speaker, Consultant, Advisor: Grail Llc. All other authors have declared no conflicts of interest.