788O Association of pre-treatment ctDNA with disease recurrence and clinical and translational factors in patients with stage IIIB-D/IV melanoma treated with adjuvant immunotherapy (CheckMate 915)

Abstract

In patients (pts) with resectable melanoma, circulating tumor DNA (ctDNA) detection post-resection may be useful to inform disease state and recurrence risk. Post-resection pre-treatment plasma from 1127 pts with stage IIIB-D/IV resected melanoma treated with nivolumab + ipilimumab vs nivolumab in the phase 3 CheckMate 915 study (NCT03068455) was retrospectively evaluated for ctDNA status and level, using a tumor-guided, pt-specific panel of up to 200 variants (Invitae Personalized Cancer MonitoringÔ). Kaplan-Meier and Cox regression models were used to evaluate the association between ctDNA status and recurrence-free survival (RFS), alone and combined with baseline clinical factors and biomarkers, including interferon-γ, TMB, tumor PD-L1, CD8+ T cells, tumor thickness, ulceration, and lymph node involvement. Overall pre-treatment ctDNA prevalence was ∼16% (95% CI: 14%–18%) and similar across most baseline demographics. A trend of greater ctDNA+ prevalence in higher stage III substages of melanoma was observed (IIIB = 11% [35/333], IIIC = 18% [110/596], IIID = 41% [13/32]). Pre-treatment ctDNA was associated with an increased risk of recurrence (HR 1.87, 95% CI: 1.48–2.36; Table). No significant interaction between ctDNA status and treatment arm was seen (ratio of hazard ratios: 0.99, 95% CI: 0.63–1.57). Patients with ctDNA present exhibited a greater rate of recurrence, seen as early as week 13 of therapy (Table). Distant metastasis-free survival results were similar. In composite analyses, improved RFS prediction was observed after combining ctDNA with clinical factors and biomarkers.Table: 788ORFS probability by pre-treatment ctDNA status in CheckMate 915 treated patientsStatusNumber of pts (n)13-week RFS (95% CI)12-month RFS (95% CI)24-month RFS (95% CI)ctDNA+18372.3% (65–78.3)58.4% (50.7–65.3)45.5% (37.9–52.8)ctDNA-94491.7% (89.7–93.3)75.1% (72.1–77.8)65.4% (62.1–68.4) Open table in a new tab Pre-treatment ctDNA was associated with increased risk of early recurrence across treatment arms. ctDNA is a useful biomarker for combined analyses predicting outcome for adjuvant melanoma.