The Association of Clinical Outcomes with Posttreatment Changes in the Relative Eosinophil Counts and Neutrophil-to-Eosinophil Ratio in Patients with Advanced Urothelial Carcinoma Treated with Pembrolizumab

Figures & data

Table 1 Patients’ Characteristics

Characteristics (n=105)
Age (years), median (IQR)	72 (67–77)
Male sex, n (%)	75 (71.4)
ECOG PS score, n (%)
0	64 (61.0)
1	31 (29.5)
≥2	10 (9.5)
Primary tumor site, n (%)
Bladder	42 (40.0)
Upper urinary tract	41 (39.0)
Upper urinary tract + bladder	22 (21.0)
Pure UC in histologic testing, n (%)	85 (81.0)
Albumin (g/dL), median (IQR)	3.8 (3.5–4.2)
LDH (U/L), median (IQR)	200 (178–237)
Number of prior chemotherapy regimens, n (%)
1	84 (80.0)
2	12 (11.4)
3	9 (8.6)
Disease site (including primary organ), n (%)
1 organ	47 (44.8)
2 organs	26 (24.8)
≥3 organs	32 (30.5)
Follow-up period (months), median (IQR)	8.4 (4.1–15.7)
Progression free survival (months), median (95% CI)	3.3 (2.8–5.5)
Overall survival (months), median (95% CI)	13.7 (10.2–19.8)

Abbreviations: IQR, interquartile range; ECOG PS, Eastern Cooperative Oncology Group Performance Status; UC, urothelial carcinoma; LDH, lactate dehydrogenase; CI, confidence interval.

Table 2 Changes in the Relative Eosinophil Count and Neutrophil-to-Eosinophil Ratio Before and Three Weeks After Pembrolizumab

Eosinophils	Controlled Disease (n=56)	Progressive Disease (n=49)	P value
Before pembrolizumab initiation
REC (%), median (IQR)	2.1 (0.8–4.9)	1.8 (0.9–4.1)	0.339
NER, median (IQR)	29.9 (11.8–79.5)	38.4 (18.0–76.1)	0.304
3 weeks later after pembrolizumab initiation
REC (%), median (IQR)	3.5 (1.6–6.3)	1.9 (0.9–4.7)	0.008
NER, median (IQR)	19.7 (8.7–37.6)	33.4 (12.6–85.2)	0.004

Note: Patients with controlled disease included those with a complete response, partial response and stable disease.

Abbreviations: REC, relative eosinophil count; IQR, interquartile range; NER, neutrophil-to-eosinophil ratio.

Figure 1 The overall survival in patients treated with pembrolizumab according to the pretreatment relative eosinophil count and neutrophil-to-eosinophil ratio. *P values are reported.

Figure 2 The overall survival in patients treated with pembrolizumab according to the change of relative eosinophil count and neutrophil-to-eosinophil ratio at three weeks after pembrolizumab. *P values are reported.

Table 3 The Univariate and Multivariate Analyses of the Factors Associated with the Overalls Survival in Patients Receiving Pembrolizumab Treatment

		Univariate		Multivariate
Variable		HR (95% CI)	p-value	HR (95% CI)	p-value
Age		0.998 (0.971–1.028)	0.911
Sex	Male	1		1
	Female	2.141 (1.244–3.687)	0.006	1.544 (0.794–3.001)	0.200
ECOG PS	0	1		1
	1	2.127 (1.173–3.855)	0.013	1.820 (0.932–3.555)	0.079
	≥2	8.654 (4.069–18.402)	<0.001	4.017 (1.618–9.975)	0.003
Primary tumor site	Bladder	1
	Upper urinary tract	1.327 (0.728–2.419)	0.356
	Bladder + upper urinary tract	1.116 (0.544–2.287)	0.765
Histology	Pure UC	1
	Mixed UC	0.750 (0.367–1.534)	0.431
Albumin	≥3.7 g/dl	1		1
	<3.7 g/dl	3.408 (1.959–5.929)	<0.001	2.744 (1.438–5.236)	0.002
LDH	<246 U/L	1		1
	≥246 U/L	2.135 (1.173–3.887)	0.013	2.436 (1.228–4.829)	0.011
Disease site (including primary organ)	1 organ	1		1
	2 organs	1.285 (0.599–2.757)	0.519	2.093 (0.891–4.921)	0.090
	≥3 organs	2.772 (1.527–5.031)	<0.001	2.324 (1.149–4.702)	0.019
Pretreatment REC	<4.8	1
	≥4.8	1.000 (0.537–1.867)	0.997
Pretreatment NER	<13.7	1
	≥13.7	1.142 (0.621–2.098)	0.669
Posttreatment REC (3 weeks later)	Increased	1		1
	Decreased	2.797 (1.643–4.763)	<0.001	31.298 (3.724–263.048)	0.002
Posttreatment NER (3 weeks later)	Decreased	1		1
	Increased	2.254 (1.327–3.829)	0.003	11.563 (1.430–93.481)	0.022

Abbreviations: ECOG PS, Eastern Cooperative Oncology Group Performance Status; UC, urothelial carcinoma; LDH, lactate dehydrogenase; REC, relative eosinophil count; NER, neutrophil-to-eosinophil ratio.