25P - Circulating tumor DNA is predictive of overall survival in patients with metastatic uveal melanoma

Background

Circulating tumor DNA (ctDNA) refers to small fragments of DNA, shed from tumor cells into the bloodstream. Measuring it can serve as a non-invasive tool for real-time monitoring of disease dynamics. CtDNA levels have been reported to be predictive of overall survival (OS) in patients with very rare metastastic uveal melanoma (MUM), treated with tebentafusp (Carvajal et el.,2022). Here, we investigate if ctDNA is predictive of progression free survival (PFS) and OS in patients with MUM treated with any therapy.

Methods

Samples from patients treated for MUM at three academic centers were analyzed using a commercially available IVDR-certified digital PCR test. This test includes an integrated analysis software to ensure standardized data analysis across samples and enables the quantification of ctDNA for GNAQ Q209L, GNAQ Q209P and GNA11 Q209L mutations. Patients with at least 2 available samples and clinical data were included.

Results

576 samples from 72 patients with rare MUM were analyzed. 37 patients had GNA11 Q209L, 19 – GNAQ Q209P, and 16 – GNAQ Q209L mutation. 37 patients had baseline samples prior to first-line treatment, 27 of which had detectable levels of ctDNA. Out of 52 patients with baseline samples prior to any line of therapy, 40 had detectable levels. In the first line cohort, non-detectable baseline ctDNA was predictive of better PFS (p = 0.02, and a hazard ratio of 0.28 with p = 0.025) and OS (p = 0.03, and a hazard ratio of 0.14 with p = 0.058). Baseline ctDNA was also predictive for PFS and OS of non first-line therapies (p = 0.03 and p = 0.01).

Conclusions

ctDNA levels have a significant predictive value for PFS and OS in metastatic uveal melanoma, treated with first or subsequent lines of therapy. It provides a non-invasive method to predict outcome.

Legal entity responsible for the study

University Medical Center Hamburg-Eppendorf and University Hospital Zürich.

Funding

Oncobit AG.

Disclosure

J. Kött: Financial Interests, Personal, Speaker’s Bureau, outside the submitted work; BMS, Sanofi, SUN Pharma, Pierre Fabre. S. Freiberger, S. Orjuela: Financial Interests, Personal, Full or part-time Employment: Oncobit AG. R. Dummer: Financial Interests, Personal, Advisory Board, outside the submitted work; Novartis, MSD, BMS, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, T3 Pharma, MaxiVAX SA, Pfizer, Simcere, touchIME. R. Sullivan: Financial Interests, Personal, Research Grant, outside the submitted work; Merck; Financial Interests, Personal, Advisory Board, outside the submitted work; Merck, Marengo, Novartis, Pfizer, Replimune. M.P. Levesque: Financial Interests, Personal, Research Funding, outside the submitted work; Roche, Novartis, Molecular Partners, Scailyte; Financial Interests, Personal, Research Funding: Oncobit. C. Gebhardt: Financial Interests, Personal, Advisory Board, outside the submitted work; Almirall, Amgen, Beiersdorf, BioNTech, BMS, Immunocore, Janssen, MSD, Novartis, Pierre Fabre, Regeneron, Roche, Sanofi, SUN Pharma, Sysmex; Financial Interests, Personal, Research Funding, outside the submitted work; BMS, Novartis, Regeneron, Sanofi. All other authors have declared no conflicts of interest.