Impact of patients’ and disease characteristics (combined variables) on treatment response and overall survival since the beginning of combined immunotherapy

Total n = 35Responder n = 15Non-Responder n = 20Response P valueOverall survival P value
Combination of TMB [Mut/Mb] and ctDNA [copies/ml] detection3
TMB > 23 Mut/Mb+ ctDNA not detectable330< 0.00011*0.0052*
TMB > 23 Mut/Mb+ ctDNA detectable330
TMB ≤ 23 Mut/Mb+ ctDNA not detectable853
TMB ≤ 23 Mut/Mb+ ctDNA detectable13013
Combination of TMB [Mut/Mb] and ctDNA [copies/ml] increase3
TMB > 23 Mut/Mb+ ctDNA not increasing440< 0.00011*0.0322*
TMB > 23 Mut/Mb+ ctDNA increasing110
TMB ≤ 23 Mut/Mb+ ctDNA not increasing1257
TMB ≤ 23 Mut/Mb+ ctDNA increasing909
Combination of TMB [Mut/Mb] and cell-free DNA [ng/ml]4
TMB > 23 Mut/Mb+ cfDNA decrease > 50%3300.0011*0.0162*
TMB > 23 Mut/Mb+ cfDNA stable110
TMB > 23 Mut/Mb+ cfDNA increase > 50%110
TMB ≤ 23 Mut/Mb+ cfDNA decrease > 50%312
TMB ≤ 23 Mut/Mb+ cfDNA stable1147
TMB ≤ 23 Mut/Mb+ cfDNA increase > 50%707
Combination of TMB [Mut/Mb] and liver metastases
TMB > 23 Mut/Mb+ no liver metastases660< 0.00011*0.0182*
TMB ≤ 23 Mut/Mb+ no liver metastases1459
TMB ≤ 23 Mut/Mb+ liver metastases1019
Combination of TMB [Mut/Mb] and sex
TMB > 23 Mut/Mb+ male6600.0021*0.0102*
TMB ≤ 23 Mut/Mb+ female927
TMB ≤ 23 Mut/Mb+ female15411

* significant (in bold).

1Exact Chi-Square Test for Trend (Monte Carlo Simulation)

2Log rank test for Trend

3ctDNA measured by tumor-specific variant [copies/ml plasma] at first follow-up after start of combined immunotherapy

4Cell-free DNA [ng/ml plasma] at first follow-up after start of combined immunotherapy