Tumor mutation burden and circulating tumor DNA in combined CTLA-4 and PD-1 antibody therapy in metastatic melanoma – results of a prospective biomarker study

Table 2 Impact of patients’ and disease characteristics on treatment response and overall survival since the beginning of combined immunotherapy

	Total n = 35	Responder n = 15	Non-Responder n = 20	Response P value	Overall survival P value
TMB [Mut/Mb]
> 23	6	6	0	0.002 ^1*	0.06²
≤ 23	24	6	18	0.002 ^1*	0.06²
ctDNA [copies/ml] detection⁵
Not detectable	14	10	4	0.011 ^1*	0.006 ^2*
Detectable	18	4	14	0.011 ^1*	0.006 ^2*
ctDNA [copies/ml] increase⁵
Not increasing	20	12	8	0.008 ^1*	0.03 ^2*
Increasing	11	1	10	0.008 ^1*	0.03 ^2*
Cell-free DNA [ng/ml]⁶
Decrease > 50%	7	5	2	0.022 ^3*	0.005 ^4*
Stable	15	7	8
Increase > 50%	9	1	8
LDH baseline elevated
No	21	11	10	0.296¹	0.001 ^2*
Yes	14	4	10	0.296¹	0.001 ^2*
Targeted therapy before
No	25	12	13	0.458¹	0.001 ^2*
Yes	10	3	7	0.458¹	0.001 ^2*
Sex
Male	19	11	8	0.087¹	0.005 ^2*
Female	16	4	12	0.087¹	0.005 ^2*
Liver metastasis baseline
No	25	14	11	0.022 ^1*	0.013 ^2*
Yes	10	1	9	0.022 ^1*	0.013 ^2*
PD-L1 Expression
≥ 1%	10	6	4	0.080¹	0.772²
< 1%	11	2	9	0.080¹	0.772²

* significant (in bold).
¹Exact Test of Fisher
²Log rank test
³Exact Chi-Square Test for Trend (Monte Carlo Simulation)
⁴Log rank test for Trend
⁵ctDNA measured by tumor-specific variant [copies/ml plasma] at first follow-up after start of combined immunotherapy
⁶Cell-free DNA [ng/ml plasma] at first follow-up after start of combined immunotherapy