Serum parameters as prognostic biomarkers in a real world cancer patient population treated with anti PD-1/PD-L1 therapy

Figures & data

Table 1. Demographic data.

	n (%)
Patients
Total	114
Female	40 (35.1)
Male	74 (64.9)
Median age (years)	60 (range 22–88)
Diagnosis
Lung cancer	35 (30.7)
Renal cancer	25 (21.9)
Head and neck cancer	11 (9.6)
Breast cancer	5 (4.4)
Colorectal cancer	5 (4.4)
Sarcoma	10 (8.8)
Urothelial cancer	12 (10.6)
Others	11 (9.6)
Prior therapy lines
0	7 (6.4)
1	33 (30.0)
2	26 (23.6)
≥3	44 (40.0)
Missing	4
Therapy
Nivolumab	55 (48.2)
Pembrolizumab	59 (51.8)
Mean cycle number (range)	6 (1 − 36)
Smoking status
Current	19 (21.1)
Former	35 (38.9)
Never	36 (40.0)
Missing	24

Figure 1. Comparison of OS by tumour entity. Heterogenity of included cancer subtype and influence on OS. HNSCC: Head and neck squamous cell carcinoma; Lung: lung cancer; Renal: renal cell carcinoma.

Figure 2. Pre-treatment serum levels and their unadjusted association with OS and PFS. (A) OS curve for LDH, (B) PFS for LDH, (C) OS curve for CRP, (D) PFS for CRP levels, (E) OS curve for serum Alb, (F) PFS curve for serum Alb, (G) OS curve for LC and (H) PFS curve for LC.

Table 2. Median OS and 25–75 percentile according to serum LDH, CRP, Alb and LC at therapy start.

	Median OS	25%–75%	Median PFS		25%–75%
LDH ≤ 250 U/l	13.6	3.9–36.5	5.0	2.0–13.0
LDH>250 U/l	3.7	0.7–13.6	2.0	0.5–4.0
CRP ≤ 0.5 mg/dl	23.3	8.6–n.r.	7.0	3.0–22.0
CRP>0.5 mg/dl	7.9	1.4–23.0	3.0	1.0–9.0
Alb ≥ 35 g/l	15.6	5.1–37.7	5.0	2.0–13.0
Alb < 35 g/l	3.3	0.6–13.3	1.5	0.5–7.0
LC ≥ 1 G/l	16.4	2.9–36.5	4.0	1.0–13.0
LC < 1 G/l	11.2	3.9–20.7	4.0	2.0–9.0

Figure 3. Univariable and multivariable analysis of the effect of baseline covariable value on OS (A) and PFS (B). Hazard ratios (with 95% confidence intervals) quantify the effect resulting from a change in the respective baseline covariable value. Effects of covariables entering the model after log-transformation refer to 20% increases, those of other variables to increases by the given units. Time-dependent effects are reported at 6, 12 and 24 months. Confidence intervals not including 1 indicate statistical significance. Both, univariable and multivariable models are stratified for tumour type.

Figure 4. Different scores and their influence on outcome parameters in cancer patients. The GPS has prognostic value regarding OS (A) and PFS (B) in our cohort of patients undergoing ICI therapy. Neutrophil to lymphcyte Ratio is strongly prognostic regarding OS (C) and PFS (D) in our cohort of patients. GRIm Score has prognostic value regarding OS (E) and PFS (F) in our cohort of patients treated with ICIs.

Table 3. Median OS and HR of predefined scores.

GPS	mOS	25%–75%	HR	95% CI	mPFS	25%–75%	HR	95% CI
Good	23.3	8.6–n.r.	1		7	2–30.8
Intermediate	14.2	5.0–37.7	1.38	0.7–2.75	5	2–12	1.41	0.76–2.64
Bad	2.3	0.6–11.4	3.57	1.76–7.25	1	0.5–6	2.70	1.39–5.27
GRIm
0–1 Low	14.7	5.3–37.7	1		5	2–13
2–3 High	1.1	0.6–7.1	2.84	1.72–4.69	1	0.5–4	2.39	1.48–3.87

mOS in month with the respective 25 + 75 percentile.

Figure 5. OS according to the individual 8-weeks change in LDH (A), CRP (B) and Alb (C) when grouped into quartiles 1–4 (Q1–Q4). Q1 representing the highest increase and Q4 the lowest increase of each serum parameter. p<.05 shows a statistically significant effect between all quartiles including a time dependent effect.

Table 4. Median OS and 25–75 percentile and HR and 95% CI for differences between baseline and 8 weeks regarding 6 month – OS for LDH, CRP and Alb.

LDH	mOS	25%–75%	LDH	HR	95% CI
Q1	2.6	1.2–10.4
Q2	16.8	9.2–34.5	Q2 vs. Q1	0.41	0.18–0.96
Q3	20.4	11.4–n.r.	Q3 vs. Q1	0.32	0.13–0.81
Q4	20.8	5.7–n.r.	Q4 vs. Q1	0.41	0.18–0.95
CRP	mOS	25%–75%	CRP	HR	95% CI
Q1	3.2	1.2–9.2
Q2	21	6.1–n.r.	Q2 vs. Q1	0.30	0.13–0.70
Q3	22.4	11.4–n.r.	Q3 vs. Q1	0.20	0.08–0.52
Q4	12.4	8.8–27.7	Q4 vs. Q1	0.47	0.22–0.99
Alb	mOS	25%–75%	Alb	HR	95% CI
Q1	17.6	9–n.r.	Q1 vs. Q4	0.77	0.27–2.17
Q2	19.9	11–29–n.r	Q2 vs. Q4	0.71	0.22–2.28
Q3	21.3	3–29.8	Q3 vs. Q4	1.15	0.40–3.33
Q4	2.4	1.2–11.4

Patients were grouped in quartiles according to LDH, CRP or Alb increase from baseline. Q1 represents patients with the highest increase of the respective serum parameter.

Data availability statement

Data and materials supporting the results are available upon reasonable request from the corresponding author TF ([email protected])