Early Circulating Tumour DNA Variations Predict Tumour Response in Melanoma Patients Treated with Immunotherapy
Laura Keller, Nicolas Guibert, Anne Casanova, Stephanie Brayer, Magali Farella, Myriam Delaunay, Julia Gilhodes, Elodie Martin, Gisèle Balagué, Gilles Favre, Anne Pradines, Nicolas Meyer
Antibodies targeting immune checkpoints were recently approved for metastatic melanoma. However, not all patients will respond to the treatment and some will experience grade III–IV immune-related adverse events. Therefore, early identification of non-responder patients would greatly aid clinical practice. Detection of circulating tumour DNA (ctDNA) is a non-invasive approach to monitor tumour response. Digital droplet PCR was used to quantify BRAF and NRAS mutations in the plasma of patients with metastatic melanoma treated with immunotherapy. In 16 patients, ctDNA variations mirrored tumour response (p = 0.034) and ctDNA augmentation during follow-up detected tumour progression with 100% specificity. In 13 patients, early ctDNA variation was associated with clinician decision at first evaluation (p = 0.0046), and early ctDNA increase with shorter progression-free survival (median 21 vs. 145 days; p = 0.001). Monitoring ctDNA variations early during immunotherapy may help clinicians rapidly to discriminate non-responder patients, allow early adaptation of therapeutic strategies, and reduce exposure to ineffective, expensive treatment.
Immunotherapy has yielded a dramatic improvement in the prognosis and survival of patients with unresectable melanoma. However, not all patients respond to treatment and some experience severe adverse events. The detection of mutations in peripheral blood (i.e. ctDNA) is a new, non-invasive approach to monitor tumour response. Using a sensitive method, this study showed that early assessment of ctDNA variation during the course of therapy could predict the tumour response to treatment. These results may help clinicians to rapidly discriminate non-responders, allowing early adaptation of therapeutic strategies and reducing their exposure to ineffective and costly treatment.