2024 AACR Podium Presentation: Advanced Melanoma on Immunotherapy, UKE

“Summary and Conclusions

Despite remarkable progress in the treatment of melanoma by immune checkpoint inhibitors (ICI), a large proportion of patients still do not respond or achieve durable clinical benefit from ICI
Circulating tumor DNA (ctDNA) monitoring in peripheral blood has shown promise for disease surveillance and prognostication of ICI response. Yet even in the metastatic context, ctDNA signals can be missed, suggesting the need for increased assay sensitivity
We used a tumor-informed ctDNA assay capable of detection down to 1 part-per-million (PPM) ctDNA to profile 188 plasma samples from 23 melanoma patients receiving ICI over several years
Residual disease was detected in ctDNA over a broad range, from 130,000 PPM down to 2.3 PPM, with approximately a third below 100 PPM and a quarter of detections below 50 PPM
Early on-treatment increases in ctDNA level, and both ctDNA-based molecular clearance (mCR) and molecular progression (mPD) were all prognostic of both OS and PFS
Additionally, mCR consistently preceded radiographic imaging
Our results show the importance and utility of an ultra-sensitive ctDNA assay in advanced melanoma treated by ICI with potential implications for other cancers”

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