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. 2019 Aug 13;36(10):2638–2678. doi: 10.1007/s12325-019-01051-z

Table 3.

Current investigational liquid biomarkers of ICB response

Marker Drug Malignancy End-point results References
LDH

Ipilimumab

Pembrolizumab

Nivolumab

Melanoma

Elevated baseline LDH = lower

ORR

P = 0.0292

Elevated baseline LDH = decreased response rate of 22.3, 95% CI (17.1–28.1) compared to 42.0, 95% CI (36.6–47.5)

Diem et al. [153]

Ribas et al. [8]

Neutrophil-lymphocyte ratio (NLR) Nivolumab NSCLC

Baseline NLR > 3 shorter PFS predictive marker at 2 and 4 weeks

P = 0.484

2 weeks P = 0.00528

4 weeks P = 0.00515

Nakaya et al. [154]
Ipilimumab Melanoma

Baseline NLR > 5 worse PFS and OS

PFS P = 0.0006

OS P < 0.0001

Ferrucci et al. [155]
Absolute eosinophil count Pembrolizumab Melanoma

High count–low response rate

P < 0.001

Weide et al. [126]
Ipilimumab Melanoma

High count–low response rate

P < 0.0001

Ferrucci et al. [127]
Monocyte count and myeloid derived suppressor cells (MDSCs) Ipilimumab Melanoma

Low baseline levels show a favorable response

P < 0.001

Martens et al. [147]
T-cell markers and sPD-L1 Ipilimumab Melanoma

High CD4(+)CD25(+)FoxP3(+)-Treg better survival

P < 0.001

Martens et al. [147]
Ipilimumab Melanoma

Increased baseline T-cell receptor diversity associated with improved response, no survival difference

P = 0.01

Postow et al. [156]
Nivolumab NSCLC

Increased SOX-2 reactive T-cells in periphery better response

P = 0.04

Dhodapkar et al. [157]

PD-1 and PD-L1

Antibodies

NSCLC

Increased PD-1, Ki-67 + CD8 T-cells 4 weeks into treatment correlated with clinical benefit.

P < 0.0001

Kamphorst et al. [158]

PD-1 and PD-L1

Antibodies

NSCLC

Baseline elevated PD-L1 as a poor prognostic marker

P = 0.002

Boffa et al. [159]

PD-1 and PD-L1

Antibodies

OSCC

Elevated PD-L1 mRNA expression in peripheral blood could contribute to increased metastatic behavior (higher grade cancer, node positive status)

P < 0.05

Weber et al. [160]

Ipilimumab

Pembrolizumab

Melanoma

High pretreatment levels of sPD-L1 were associated with increased likelihood of progressive disease

P = 0.0015

Zhou et al. [50]
B cell-antibody markers Ipilimumab Melanoma

NYESO antibody seropositive have better ORR

P = 0.02

Yuan et al. [161]
Ipilimumab Melanoma

Soluble CTLA4 antibody associated with improved response

P = 0.02

Leung et al. [162]
Soluble CD25 Ipilimumab Melanoma

Elevated baseline CD25 associated with shorter OS

P = 0.056

Hannani et al. [144]
bTMB Atezolizumab NSCLC

bTMB correlated with TMB, bTMB correlated with PFS, bTMB did not associate with high PD-L1 expression

bTMB P = 0.035

PD-L1 P = 0.160

Gandara et al. [41]

NSCLC non-small cell lung carcinoma, LDH lactate dehydrogenase, OSCC oral squamous cell cancer, ORR objective response rate, OS overall survival, PFS progression-free survival, bTMB blood–tumor mutational burden, sPD-L1 soluble PD-L1