A Novel and Validated Inflammation-Based Prognosis Score (IBPS) Predicts Outcomes in Patients with Diffuse Large B-Cell Lymphoma

Figures & data

Table 1 Construction and an Optimal Cut-Off Value of Each Indicator

Scoring Systems	Cut-Off value
Neutrophil to lymphocyte ratio (NLR)
Neutrophil count (×10^9/L): lymphocyte count (×10^9/L)	4.03
Platelet to lymphocyte ratio (PLR)
Platelet count (×10^9/L): lymphocyte count (×10^9/L)	201.75
Lymphocyte-to-monocyte ratio (LMR)
Lymphocyte count (×10^9/L): monocyte count (×10^9/L)	1.91
Albumin to globulin ratio (AGR)
Albumin (g/L): globulin (g/L)	1.48
C-reactive protein to albumin ratio (CAR)
C-reactive protein (g/L): albumin (g/L)	0.32
Systemic immune-inflammation index (SII)
Platelet count (×10^9/L) × neutrophil count (×10^9/L)/lymphocyte count (×10^9/L)	878.73
System inflammation response index (SIRI)
Monocyte count (×10^9/L) × neutrophil count (×10^9/L)/lymphocyte count (×10^9/L)	1.38
Prognostic Nutritional Index (PNI)
Albumin (g/L) +5 × total lymphocyte count ×10^9/L	43.55
Modified Glasgow Prognostic Score (mGPS)	Score
C-reactive protein ≤10 mg/L	0
C-reactive protein >10 mg/L and albumin ≥35 g/L	1
C-reactive protein >10 mg/L and albumin <35 g/L	2

Table 2 Baseline Characteristics of Patients

Characteristic	Training Set N (%)	Validation Set N (%)	p
Age(years)			0.423
≤60 years	92(43.2)	34(38.2)
>60 years	121(56.8)	55(61.8)
Gender			0.928
Male	105(49.3)	44(49.4)
Female	108(50.7)	45(50.6)
Ann Arbor stage			0.232
I/II	107(50.2)	38(42.7)
III/IV	106(49.8)	51(57.3)
LDH level(U/L)			0.550
≤245	144(67.6)	57(64.0)
>245	69(32.4)	32(36.0)
EN site involvement			0.121
<2EN sites	162(76.1)	60(67.4)
≥2 EN sites	51(23.9)	29(32.6)
ECOG PS			0.345
0–1	188(88.3)	75(84.3)
≥2	25(11.7)	14(15.7)
B symptoms			0.093
Yes	35(16.4)	22(24.7)
No	178(83.6)	67(75.3)
COO(Hans)			0.960
GCB	94(44.1)	39(43.8)
Non-GCB	119(55.9)	50(56.2)
Response			0.074
CR+PR	183(85.9)	69(77.5)
SD+PD	30(14.1)	20(22.5)
Combined operation			0.313
Yes	80(37.6)	28(31.5)
No	133(62.4)	61(68.5)
Combined radiotherapy			0.567
Yes	57(26.8)	21(23.6)
No	156(73.2)	68(76.4)
NLR			0.663
<4.62	149(70.0)	60(67.4)
≥4.62	64(30.0)	29(32.6)
PLR			0.284
<192.06	139(65.3)	64(71.9)
≥192.06	74(34.7)	25(28.1)
LMR			0.004
<2.62	57(26.8)	39(43.8)
≥2.62	156(73.2)	50(56.2)
AGR			0.006
<1.48	106(49.8)	29(32.6)
≥1.48	107(50.2)	60(67.4)
CAR			0.224
<0.32	156(73.2)	59(66.3)
≥0.32	57(26.8)	30(33.7)
SII			0.531
<1109.90	149(70.0)	59(66.3)
≥1109.90	64(30.0)	30(33.7)
SIRI			0.261
<1.50	118(55.4)	43(48.3)
≥1.50	95(44.6)	46(51.7)
PNI			0.389
<42.55	75(35.2)	36(40.4)
≥42.55	138(64.8)	53(59.6)
mGPS			0.287
0	151(70.9)	57(64.0)
1	34(12.0)	14(15.7)
2	28(13.1)	18(20.2)
β-2 MG			0.494
<2.55	152(71.4)	60(67.4)
≥2.55	61(28.6)	29(32.6)
MYC			0.179
Negative	75(35.2)	23(25.8)
Positive	64(30.0)	26(29.2)
Unknown	74(34.7)	40(44.9)
BCL2			<0.001
Negative	75(35.2)	28(31.5)
Positive	123(57.7)	45(50.6)
Unknown	15(7.0)	16(17.9)
Ki67			0.964
<90%	137(64.3)	57(64.0)
≥90%	76(35.7)	32(36.0)
IPI			0.006
Low	102(47.9)	39(42.7)
Low-intermediate	50(23.5)	18(20.2)
High-intermediate	47(22.1)	15(16.9)
High	14(6.6)	18(20.2)
NCCN-IPI			0.029
Low	33(15.5)	13(14.6)
Low-intermediate	112(52.6)	38(42.7)
High-intermediate	59(27.7)	26(29.2)
High	9(4.2)	12(13.5)

Abbreviations: AGR, albumin to globulin ratio; COO, cell of origin; CAR, C-reactive protein to albumin ratio; CR, complete remission; EN, extranodal; ECOG PS, Eastern Cooperative Oncology Group Performance Status; GCB, germinal center B-cell-like; IPI, International Prognostic Index; LDH, lactate dehydrogenase; LMR, lymphocyte to monocyte ratio; mGPS, modified Glasgow prognostic score; NCCN, National Comprehensive Cancer Network; NLR, neutrophil to lymphocyte ratio; PR, partial remission; PD, progressive disease; PLR, platelet to lymphocyte ratio; PNI, prognostic nutritional index; SD, stable disease; SIRI, system inflammation response index; SII, systemic immune-inflammation index; β-2 MG, β-2 microglobulin.

Table 3 Hazard Ratio (HR) and Regression Coefficient (β) of Each Index and Corresponding Score

Factor	HR (95% CI)	β (HR = e^β)	P-value	Score
SII≥873.73	3.054(1.550–6.017)	1.116	0.001	1
PNI<43.55	3.056(1.378–6.778)	1.117	0.006	1
mGPS			0.027
mGPS=1	1.413(0.591–3.379)	0.346	0.437	0
mGPS=2	2.782(1.315–5.884)	1.023	0.007	1

Abbreviations: CI, confidence interval; HR, hazard ratio; mGPS, modified Glasgow prognostic score; PNI, Prognostic nutritional index; SII, Systemic immune-inflammation index.

Figure 1 The least absolute shrinkage and selection operator (LASSO) Cox regression model was used to select the elements to build inflammation-based prognosis score (IBPS), and the Kaplan–Meier analysis was used to generate survival curves between different IBPS groups. (A) A correlation matrix with correlation coefficients from −1 (negative correlation; red) to 1 (positive correlation; blue). (B) The LASSO coefficient profiles of inflammatory biomarkers. (C) Tuning parameter (λ) selection cross-validation error curve. (D) Survival curves in the training cohort (E) Survival curves in the validation cohort.

Table 4 Univariate and Multivariate Analysis of the Training and Validation Cohorts

Variable	Univariate				Multivariate
	Training Cohort (n = 213)		Validation Cohort (n = 89)		Training Cohort (n = 213)		Validation Cohort (n = 89)
	Hazard Ratio (95% CI)	P	Hazard Ratio (95% CI)	P	Hazard Ratio (95% CI)	P	Hazard Ratio (95% CI)	P
Age >60 (years)	2.172(1.118–4.221)	0.022	4.820(2.067–8.403)	0.001	1.469(0.740–2.917)	0.272	2.148(0.665–6.938)	0.201
Sex (male)	1.657(0.902–3.042)	0.104	1.275(0.644–2.525)	0.486
ECOG PS ≥2	3.243(1.668–6.302)	<0.001	6.132(2.882–13.046)	<0.001	3.136(1.414–6.956)	0.005	4.581(1.942–10.804)	0.001
LDH > 245 (U/L)	3.773(2.066–6.892)	<0.001	2.429(1.223–4.825)	0.011	1.767(0.851–3.672)	0.127	1.485(0.682–3.234)	0.320
Ann Arbor stage, III–IV	1.862(1.007–3.443)	0.047	2.350(1.060–5.211)	0.036	1.033(0.521–2.047)	0.927	0.871(0.330–2.297)	0.779
No. of extranodalsites ≥2	1.616(0.856–3.050)	0.139	1.648(0.818–3.321)	0.162
COO (non-GCB subtype)	1.071(0.590–1.947)	0.821	1.875(0.908–3.873)	0.089			0.959(0.380–2.418)	0.929
B symptoms	2.001(1.030–3.887)	0.041	1.550(0.751–3.200)	0.236	0.962(0.448–2.064)	0.921
β2MG > 2.50 mg/L	3.433(1.897–6.248)	<0.001	2.130(1.073–4.231)	0.031	0.934(0.432–2.022)	0.863	0.850(0.378–1.910)	0.695
Response (SD+PD)	4.955(2.675–9.177)	<0.001	5.813(2.925–11.554)	<0.001	4.191(2.059–8.528)	<0.001	3.046(1.363–6.805)	0.007
Combined operation	0.393(0.189–0.817)	0.012	0.368(0.151–0.893)	0.027	0.413(0.190–0.898)	0.026	0.410(0.162–1.033)	0.059
Combined radiotherapy	1.497(0.810–2.769)	0.198	1.329(0.632–2.796)	0.453
IBPS ≥2	11.445(5.950–22.016)	<0.001	4.168(2.067–8.403)	<0.001	7.297(3.523–15.113)	<0.001	2.264(1.013–5.058)	0.046

Abbreviations: CI, confidence interval; COO, cell of origin; ECOG PS, Eastern Cooperative Oncology Group Performance Status; GCB, germinal center B-cell-like; HR, hazard ratio; IBPS, inflammation-based prognosis score; LDH, lactate dehydrogenase; PD, progressive disease; SD, stable disease; β2MG, β-2 microglobulin.

Figure 2 The nomogram for predicting the overall survival (OS) in patients with diffuse large B-cell lymphoma (DLBCL). The total points are calculated as the sum of the individual scores of each of the four variables included in the nomogram.

Figure 3 Receiver operating characteristic (ROC) verified the predictive value of nomogram, International Prognostic Index (IPI), and National Comprehensive Cancer Network (NCCN)-IPI in different sets. (A) ROC for 1-year OS in the training set; (B) ROC for 3-year OS in the training set; (C) ROC for 5-year OS in the training set; (D) ROC for 1-year OS in the validation set; (E) ROC for 3-year OS in the validation set; (F) ROC for 5-year OS in the validation set.

Figure 4 Calibration plot of the 1-, 3-, and 5-year OS nomogram in training and validation sets. (A) 1-year OS in the training set; (B) 3-year OS in the training set; (C) 5-year OS in the training set; (D) 1-year OS in the validation set; (E) 3-year OS in the validation set; (F) 5-year OS in the validation set.

Figure 5 Clinical net benefits and risk stratification of nomogram. (A) Net benefit curves based on nomogram as compared with IPI and NCCN-IPI model in the training set; (B) Net benefit curves based on nomogram as compared with IPI and NCCN-IPI model in the validation set; (C) The survival curves for OS based on the prediction of nomogram in the training set; (D) The survival curves for OS based on the prediction of nomogram in the validation set.

Figure 6 Kaplan–Meier curve of OS of DLBCL patients in different subgroups stratified according to risk stratification system in the training cohort. (A) OS of age >60; (B) OS of Ann Arbor Stage III/IV; (C) OS of LDH≥ 245U/L; (D) OS of BCL2 ≥50%; (E) OS of MYC ≥40%; (F) OS of MYC ≥40% and BCL2 ≥50%.

Data Sharing Statement

Data can be made available by contacting the corresponding author.