Circulating Tumor DNA (ctDNA) Clearance After Immune Checkpoint Inhibition (ICI) with Radiotherapy (RT) as a Prognostic Biomarker for Advanced Melanoma
Alyssa K. Steimle, Amir M. Forati, Alice Y. Zhou, Trevor McCracken, Meena M. Hosny, Golbarg Rahimi, Janmesh D. Patel, Caroline Burkey, Jessica Caraway, Taylor Huppe, Andrew Wood, Madison S. Harris, Alexander Birbrair, Jose M. Ayuso, Deepak M. Sahasrabudhe, Fauzia Hollnagel, Gary C. Doolittle, Adam R. Burr, Nina S. Mathew, Gino K. In, Adrienne Victor, Vincent T. MaBackground/Objectives: ctDNA is evolving as an important biomarker for prognostic assessment in advanced melanoma. However, the utility of ctDNA monitoring during concurrent ICI with RT remains incompletely explored. Methods: In this multicenter retrospective study, patients with unresectable stage III/IV melanoma treated with ICI and palliative RT were identified. Patients had retrospectively collected, tumor-informed, exome-based, ctDNA monitoring within 3 months following RT. Results: A total of 50 patients treated with ICI and palliative RT were analyzed. Compared with ctDNA clearance, ctDNA detectable and increasing was associated with worse OS (adjusted HR 2.52, 95% CI 1.20–5.29; p = 0.015), whereas ctDNA detectable and decreasing was not significantly different from ctDNA clearance (adjusted HR 1.58, 95% CI 0.69–3.65; p = 0.282). One-year OS was 87.5% with persistently undetectable ctDNA, 83.3% for ctDNA clearance, 46.3% for detectable and decreasing ctDNA, and 21.4% for detectable and increasing ctDNA. In a multivariable analysis, detectable and increasing ctDNA was associated with worse OS compared with ctDNA clearance (HR 2.52, 95% CI, 1.20–5.29, p = 0.015). Conclusions: Among patients with advanced melanoma treated with ICI and palliative RT, ctDNA clearance is associated with significantly improved OS compared to patients with detectable and increasing ctDNA within 3 months following RT. Ongoing prospective studies are needed to understand the role of ctDNA in this population.