Circulating Tumour DNA in Advanced Melanoma Patients Ceasing PD1 Inhibition in the Absence of Disease Progression

SIMPLE SUMMARY: Immunotherapy is an effective treatment that harnesses the immune system to fight cancer. Drugs such as immune checkpoint inhibitors have demonstrated efficacy in the treatment of advanced melanoma. However, the optimal duration of treatment is not well established. The aim of our retrospective study was to analyse the outcomes of patients who have stopped immunotherapy treatment for advanced melanoma after durable disease control. Furthermore, we assessed circulating tumour DNA (ctDNA), which is shed from the tumour into the bloodstream, to determine its validity as a predictive biomarker of disease progression after treatment was stopped. We demonstrated that stopping treatment after durable disease control results in excellent short- to medium-term prognosis and ctDNA present at the time of stopping treatment is a strong predictor of disease recurrence. ABSTRACT: Immunotherapy is an important and established treatment option for patients with advanced melanoma. Initial anti-PD1 trials arbitrarily defined a two-year treatment duration, but a shorter treatment duration may be appropriate. In this study, we retrospectively assessed 70 patients who stopped anti-PD1 therapy in the absence of progressive disease (PD) to determine clinical outcomes. In our cohort, the median time on treatment was 11.8 months. Complete response was attained at time of anti-PD1 discontinuation in 61 (87%). After a median follow up of 34.2 months (range: 2–70.8) post discontinuation, 81% remained disease free. Using ddPCR, we determine the utility of circulating tumour DNA (ctDNA) to predict progressive disease after cessation (n = 38). There was a significant association between presence of ctDNA at cessation and disease progression (p = 0.012, Fisher’s exact test) and this conferred a negative and positive predictive value of 0.82 (95% CI: 0.645–0.930) and 0.80 (95% CI 0.284–0.995), respectively. Additionally, dichotomised treatment-free survival in patients with or without ctDNA at cessation was significantly longer in the latter group (p < 0.001, HR: 0.008, 95% CI: 0.001–0.079). Overall, our study confirms that durable disease control can be achieved with cessation of therapy in the absence of disease progression and undetectable ctDNA at cessation was associated with longer treatment-free survival.