Circulating tumor DNA is a prognostic biomarker in metastatic melanoma patients treated with chemoimmunotherapy and BRAF inhibitor

Figures & data

Figure 1. PFS and OS according to pretreatment ctDNA levels (MAF ≥3% vs. <3%) (A and B) and ctDNA levels at the time of best objective response (MAF >0% vs 0%) (C and D) for all 19 ctDNA patients.

Table 1. Multivariable Cox regression models for progression-free survival and overall survival.

	HR	95% CI	p Value
Risk factor (progression-free survival)
Age ≥ 60 (vs < 60)	1.7	0.42–6.48	0.47
Male (vs female)	5.2	1.04–26.03	0.045
Non-BRAF mutation (vs BRAF mutation)	6.5	1.53–27.56	0.011
Higher M-stage (M1d vs M1c vs M1b vs M1a)	0.8	0.39–2.09	0.67
Elevated LDH (vs normal LDH)	4.0	0.90–18.10	0.068
Inferior ECOG PS (ECOG ≥ 2 vs 1 vs 0)	1.5	0.43–5.31	0.52
Pretreatment MAF ≥ 3% (vs < 3%)	6.1	1.49–24.57	0.012
Risk factor (progression-free survival)
Age ≥ 60 (vs < 60)	1.5	0.32–6.98	0.60
Male (vs female)	2.7	0.32–21.88	0.35
Non-BRAF mutation (vs BRAF mutation)	14.8	1.85–118.66	0.011
Higher M-stage (M1d vs M1c vs M1b vs M1a)	0.41	0.13–1.37	0.15
Elevated LDH (vs normal LDH)	2.7	0.38–18.55	0.32
Inferior ECOG PS (ECOG ≥ 2 vs 1 vs 0)	2.6	0.58–11.87	0.21
detectable ctDNA at BOR (vs undetectable)	26.8	2.38–301.77	0.008
Risk factor (overall survival)
Age ≥ 60 (vs < 60)	2.4	0.37–15.64	0.36
Male (vs female)	1.2	0.28–5.51	0.79
Non-BRAF mutation (vs BRAF mutation)	2.5	0.58–10.6	0.22
Higher M-stage (M1d vs M1c vs M1b vs M1a)	0.9	0.33–2.26	0.77
Elevated LDH (vs normal LDH)	2.0	0.50–7.87	0.33
Inferior ECOG PS (ECOG ≥ 2 vs 1 vs 0)	1.4	0.34–5.54	0.65
No subsequent therapy (vs yes)	1.3	0.23–7.31	0.76
Pretreatment MAF ≥ 3% (vs < 3%)	14.6	2.24–95.46	0.005
Risk factor (overall survival)
Age ≥ 60 (vs < 60)	0.9	0.12–7.09	0.93
Male (vs female)	1.3	0.20–8.53	0.79
Non-BRAF mutation (vs BRAF mutation)	1.5	0.21–10.58	0.69
Higher M-stage (M1d vs M1c vs M1b vs M1a)	0.43	0.14–1.35	0.15
Elevated LDH (vs normal LDH)	6.2	0.63–61.21	0.12
Inferior ECOG PS (ECOG ≥ 2 vs 1 vs 0)	2.7	0.39–18.70	0.32
No subsequent therapy (vs yes)	0.75	0.070–8.08	0.82
detectable ctDNA at BOR (vs undetectable)	25.1	2.75–227.44	0.004

HR: hazard ratio; CI: confidence interval.

Data availability statement

Data are available upon reasonable request to corresponding author.